Abstract: Objective To determine the mechanism of MP (morphine preconditioning) on brain ischemic/hypoxic tolerance in the hippocampus slices of mice. Methods Hippocampus slices were exposed to OGD (oxygen–glucose deprivation) to mimic ischemia-reperfusion injury in vitro. The slice injuries were assessed by both lactic dehydrogenase (LDH) release rate and cell survival rate of slices (2,3,5-triphenyltetrazolium chloride (TTC) to evaluate the protective effects of MP. Western blot analysis was used to identify the expression of PKC???Results In the hippocampal slices preconditioned with morphine, cell survival rate was increased and LDH release rate was decreased significantly compared with OGD 5min，10min and 20min (P<0.05). Immediately and at the end of 2 h reperfusion after OGD 10 min, the particulate fraction of PKC? increased significantly, concomitantly with a corresponding decrease in the cytosolic fraction (P<0.05). The increased membrane translocation of PKC? could not be inhibited by MP. Conclusion MP can reduce OGD-induced neuronal injuries, the protective effects were observed for periods of OGD equal to or shorter than 20min. PKC? membrane translocation might not be involved in the neuroprotection.