We showed the inhibitory effect of oleic and palmitoleic acids (OA and POA) on this trans10, cis12 (10t, 12c)-CLA induced cytotoxic activity. When cells were cultured in the presence of 10t, 12c-CLA, this potent cytotoxic effect on dRLh-84 cells was clearly obvious when compared to the control vehicle group. It was revealed that the levels of cellular OA and POA levels decreased upon cis9, trans11 (9c,11t) or 10t, 12c-CLA treatment in a time course dependent manner. OA or POA demonstrates a dose dependent inhibition of the 10t, 12c-CLA induced cytotoxicity. Notable nuclear fragmentation or activation of caspase-3 and 9 by 10t, 12c-CLA in dRLh-84 was counteracted by treatment with OA or POA. Results also suggest that 10t, 12c-CLA induced apoptosis can be inhibited by treatment with OA or POA.