AIM: To investigate the effect of Zhongfeng Nao De Ping, a traditional chinese medicine, on the cerebral ischemia/reperfusion injury in rats. METHODS: Delayed neuronal death (DND) model was established by bilateral carotid arteries occlusion for l0 min followed by 1 day and 7 days reperfusion. Effects of sodium glutamate, ketamine and Zhongfeng Nao De Ping on DND in the hippocampus was examined by counting neuronal density in CAl Sector, and the contents of Ca 2+ and amino acids in the hippocampus were also measured. RESULTS: The contents of the glutamate and aspartate in the hippocampus were increased significantly at l0 min after transient cerebral ischemia. Sodium glutamate markedly decreased the neuronal density in hippocampal CAl sector, while ketamine and Zhongfeng Nao De Ping increased it significantly in the same sector. The level of Ca 2+ increased on day 1, day 7 after the reperfusion, while Zhongfeng Nao De Ping inhibited the increase in Ca 2+ concentration in hippocampus. CONCLUSION: These results suggested that Zhongfeng Nao De Ping has an effective protection against DND in hippocampus following cerebral ischemia/reperfusion in rats.