Cis9, trans11 and trans10, cis12-CLA are two major isomers of conjugated linoleic acid, which have stronger activities of anti-tumor. Based the previous studies, it was explored the pathway and mechanism of inducing apoptosis in human breast cancer cell line SKBR3 by c9, t11-CLA and t10, c12-CLA. It was confirmed that CLA could increase obviously the transcription and protein expression levels of PPARγ by RT-PCR and Western blot. The synchronism and correlation between PPARγ and apoptotic proteins Bax, Bcl-2, caspase3 changes were found with a dose- and time-dependent manner. PPARγ inhibitor GW9662 experimental result showed that there is cooperative relation between them. This is the first report that CLA induces apoptosis in SKBr3 cell by the signal pathway of PPARγ-Bcl-2-Caspase3. These observations indicated that CLA will be useful for clinic therapy of anti-tumor as a new regulator of PPARγ in the future.