Aim To investigate the effects of harpagide on cerebral ischemia and the mitochondria mediated Caspase dependent apoptotic signaling pathway in mice.Methods The MCAO was employed to establish MCAO model.When the models were established, the mice were given harpagide (4, 8, 12 mg·kg-1) and edaravone (3.2 mg·kg-1) [0.1 ml·(10 g)-1] by tail vein injection after MCAO immediately.And the model and control mice were given equivalent normal saline by the same way.After MCAO for 6 h, the behavior, volume of cerebral ischemia and pathological changes in the brain were observed.Westernblot was employed to determine the contents of Cyt C in mitochondrion and pro-caspase-3 in endochylema.Results Compared with the model group, harpagide (4, 8, 12 mg·kg-1) could significantly decrease the increased nerve functional score, brain index, brain water content and volume of cerebral ischemia induced by cerebral ischemia.Harpagide (4, 8, 12 mg·kg-1) could reduce the contents of Cyt C in mitochondrion and pro-caspase-3 in endochylema.Conclusion Harpagide may have protective effect on the cerebral ischemia injury in mice, which might be related to the inhibition of the cerebral mitochondria mediated Caspase dependent apoptotic signaling pathway.