Objective: To investigated the protective effects of pachymic acid on okadaic acid(OA)-induced neurotoxicity in PC12 cells and identified a potential mechanism. Methods: Pachymic acid (10， 15， 20 μg/mL) was used as protective drugs to protect PC12 cells injured by OA (40 nmol/L). Cell viability， LDH released， intracellular Ca2+ concentration and caspase-3 activity were detected. The levels of bax and p-taus202 were detected by western blotting. Results: Compared with the control group， PC12 cells treated with 40 nmol/L OA was significantly decreased the viability to (64±3.6)% (P＜0.01)， increased the release of LDH to (141.3±3.1)% increased intracellular Ca2+ concentration to (123.5±5.2)% and caspase-3 activity to (257.0±22.8)% (P＜0.01)； compared with the model group， 50 μg/mL pachymic acid significantly increased cell viability to (90.5±3.3)% (P＜0.01)， decreased LDH released to (117.5±3.8)%， decreased [Ca2+]i， to (123.5±5.2)% and reduced caspase-3 activity to(120.0±4.1)% (P＜0.01). Western blot results confirmed that OA increased the protein expression of bax and p-taus202， pachymic acid down-regulated the expression of bax and p-taus202. Conclusion: the protective effect of pachymic acid against OA-induced apoptosis in PC12 cells was related to the inhibition of tau hyperphosphorylation.