Introduction: Ischemia induces physiological alterations in neurons which leading to cell death. Certain areas of the brain such as the hippocampus are more sensitive to ischemia. This study investigated the effects of pre-ischemic exercise on CA3 neurons. Methods: Rats were divided into three groups. Animals of exercise group were trained 5 days a week for 4 weeks. Ischemia was induced by occlusion of both common carotid arteries (CCA) for 20 minutes. Apoptotic cell death was detected by TUNEL assay.Furthermore, expression of differrent proteins determined by immunohistochemical staining. Results: The number of TUNEL-positive cells was significantly increased in ischemia group, but pre-ischemic exercise significantly reduced apoptotic cell death (P<0.001). In addition, our results showed a significant increase in Bax/Bcl-2 ratio of ischemia group. Pre-ischemic exercise attenuated this ratio by increasing Bcl-2 expression without any change in Bax level (P<0.05). Furthermore, the number of active Caspase-3-positive neurons was significantly increased in ischemia group, which was reduced markedly by exercise preconditioning (P<0.05). Conclusion: This study showed that pre-ischemic exercise can exert neuroprotective effects against ischemia in CA3 neurons.