Abstract: To investigate the inhibitory effect of Genistein(Gen)on Aβ_25-35-induced neurotoxicity and to elucidate the underlying mechanism in cultured rat pheochromocytoma(PC12)cells. The injured PC12 cells were treated with Gen and its antagonist, Myr. The influence on the expression of Bcl-2 and Bax mRNA levels was detected by RT-PCR. Cell viability was assessed by staining with Hoechst 33342/PI. Protein kinase C(PKC)activity was measured with the intervention of Gen and PKC inhibitor(Myr). The results showed that Gen could increase the Bcl-2 expression, decrease the Bax expression, increase the ratio of Bcl-2/Bax, and significantly increase cell viability, as well as the activity of PKC in Aβ_25-35-treated PC12 cells. Myr, a PKC inhibitor, partially blocked the activation effect of Gen. Gen exerted protective effect on Aβ_25-35-induced neurotoxicity via activating the PKC signaling pathway, which further regulated the Bcl-2/Bax expression.