Objective To investigate the effects of inhibition of adenosine monophosphate -activated protein kinase (AMPK) on expressions of cytochrome c (CytC) and caspase -3 and apoptosis in the cerebral cortex after cerebral ischemia-reperfusion injury in mice. Methods Thirty-six male C57BL/6 mice w ere randomly divided into three groups, a sham operation group, a ischemia -reperfusion group, and a AMPK inhibitor group, 12 in each group. A model of middle cerebral artery occlusion w as induced by suture method. The AMPK inhibitor compound C ( 20 mg/kg) w as injected intraperitonealy in the AMPK inhibitor group, the equal volume normal saline w as injected intraperitonealy in the sham operation group and the ischemia-reperfusion group w hen a thread w as inserted. Immunohistochemical staining w as used to detect the expression levels of CytC and caspase-3 and TUNEL method w as used to detect apoptosis at 24 h after ischemia-reperfusion. Results Compared w ith the ischemia-reperfusion group, the numbers of CytC (28.86 ±9.65/HP vs.58.86 ±9.65/HP; t = 7.615, P = 0.030 ) and caspase-3 (7.16 ±5.85/HP vs. 14.36 ±7.85/HP; t =2.548, P =0.035), and TUNEL (67.14 ±8.55/HP vs.95.00 ±13.51/HP; t = 6.891, P = 0.030) positive cels in the cerebral cortex w ere reduced significantly in the AMPK inhibitor group. Conclusion Inhibition of AMPK activity after cerebral ischemia-reperfusion may decrease apoptosis by dow nregulating the expressions of CytC and caspase -3, and play a neuroprotective effect.