Aim To investigate effects of calpain inhibitor calpeptin against hypoxia/glucose deprivation injury in rat hippocampal slices.Methods Forty hippocampal slices were randomly divided into two groups:Control group and calpeptin group.Calpeptin group then divided again into 1 ?mol?L-1 group,10 ?mol?L-1 group,100 ?mol?L-1 group and 200 ?mol?L-1 group according to the concentration of calpeptin in ACSF_ OGD(n=8 per group).By using electrophysiology method,changes of OPS and HIP during hypoxia/glucose deprivation process and effects of different concentration of calpeptin on it were observed.We also observed the neuronal apoptosis in hippocampal CA1 region after hypoxia/glucose deprivation and effects of different concentration of calpeptin on it.Results The HIP appearance rate and neuronal apoptosis in hippocampal CA1 region of 10 ?mol?L-1 group,100 ?mol?L-1 group and 200?mol?L-1 group significantly reduced,the OPS recovery amplitude and OPS recovery rate significantly increased,and every index among 10 ?mol?L-1 group,100 ?mol?L-1 group and 200 ?mol?L-1 group had no significant difference.Conclusion(10～200)?mol?L-1 calpeptin improved the hypoxia/glucose deprivation induced brain injury of rat hippocampal slices and the mechanism might be related to the inhibition of the neuronal apoptosis by calpeptin.