-----BEGIN PRIVACY-ENHANCED MESSAGE-----
Proc-Type: 2001,MIC-CLEAR
Originator-Name: webmaster@www.sec.gov
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MIC-Info: RSA-MD5,RSA,
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<SEC-DOCUMENT>0000874015-08-000006.txt : 20080104
<SEC-HEADER>0000874015-08-000006.hdr.sgml : 20080104
<ACCEPTANCE-DATETIME>20080104212052
ACCESSION NUMBER:		0000874015-08-000006
CONFORMED SUBMISSION TYPE:	4
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20080101
FILED AS OF DATE:		20080104
DATE AS OF CHANGE:		20080104

ISSUER:		

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ISIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	BUSINESS ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008

REPORTING-OWNER:	

	OWNER DATA:	
		COMPANY CONFORMED NAME:			PARSHALL B LYNNE
		CENTRAL INDEX KEY:			0001073385

	FILING VALUES:
		FORM TYPE:		4
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		08513590

	BUSINESS ADDRESS:	
		BUSINESS PHONE:		760-931-9200

	MAIL ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
</SEC-HEADER>
<DOCUMENT>
<TYPE>4
<SEQUENCE>1
<FILENAME>edgar.xml
<DESCRIPTION>PRIMARY DOCUMENT
<TEXT>
<XML>
<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0202</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2008-01-01</periodOfReport>

    <issuer>
        <issuerCik>0000874015</issuerCik>
        <issuerName>ISIS PHARMACEUTICALS INC</issuerName>
        <issuerTradingSymbol>ISIS</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001073385</rptOwnerCik>
            <rptOwnerName>PARSHALL B LYNNE</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O ISIS PHARMACEUTICALS, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>1896 RUTHERFORD ROAD</rptOwnerStreet2>
            <rptOwnerCity>CARLSBAD</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92008</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>Director, COO</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2008-01-01</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2008-01-01</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F1"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>876</value>
                    <footnoteId id="F1"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>8.3045</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>6569</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value></value>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Employee Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>15.38</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2008-01-02</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2008-01-02</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>91520</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2009-01-02</value>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <value>2015-01-01</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>91520</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>91520</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value></value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Employee Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>5.80</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2008-01-03</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2008-01-03</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>G</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>20000</value>
                    <footnoteId id="F3"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2006-01-03</value>
                <footnoteId id="F4"/>
            </exerciseDate>
            <expirationDate>
                <value>2012-01-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>20000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>10263</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value></value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Employee Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>5.80</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2008-01-03</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2008-01-03</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>G</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>10000</value>
                    <footnoteId id="F3"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2008-01-03</value>
            </exerciseDate>
            <expirationDate>
                <value>2012-01-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>10000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>10000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By daughter</value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Employee Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>5.80</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2008-01-03</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2008-01-03</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>G</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>10000</value>
                    <footnoteId id="F3"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2008-01-03</value>
            </exerciseDate>
            <expirationDate>
                <value>2012-01-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>10000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>10000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By daughter</value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Reporting 876 shares acquired under the Isis Pharmaceuticals, Inc. 2000 Employee Stock Purchase Plan on January 1, 2008.</footnote>
        <footnote id="F2">Grant of 1-2-08 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan.  25% of the shares subject to the option will vest and become exercisable on 1-2-09.  Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 22,880 shares per year.  The option is exercisable as to 0 shares on 1-2-08.</footnote>
        <footnote id="F3">The reporting person transferred options to her two daughters (one is a minor) who share reporting person's household, divided equally.</footnote>
        <footnote id="F4">Stock option under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan.  25% of the shares subject to the option vested and became exercisable on 1-3-06.  Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 7,565 shares per year.  The option was exercisable as to 22,698 shares on 1-3-08 prior to the reported transfer.</footnote>
    </footnotes>

    <remarks></remarks>

    <ownerSignature>
        <signatureName>/s/B. Lynne Parshall</signatureName>
        <signatureDate>2008-01-04</signatureDate>
    </ownerSignature>
</ownershipDocument>
</XML>
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
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