Abstract: Objective To investigate the levels of MEF2C phosphorylation (activation) and protein expression, and further clarify the possible mechanism following ischemia-reperfusion in hippocampal CA1 region of rat Methods Brain ischemia was induced by four-vessel occlusion in SD rats. Protein levels were determined by using Western blotting. Results MEF2C was significantly activated with a peak at 6h of reperfusion, but its protein expression level decreased in the late phase of reperfusion (3-5d). The elevation of activated (17 ka) and the inactivated forms (32 ka) of caspase-3 proteases were remarkable during 1-5d of reperfusion. In addition, Ac-DEVD-CHO, a specific inhibitor of caspase-3, could up-regulate MEF2C protein level of 3d reperfusion. SB202190 (an inhibitor of p38), but not ERK5-antisense oligonucleotides, not only inhibited MEF2C activation of 6h reperfusion but also apparently prevented the increase of caspase-3 activation caused by 3d reperfusion. Conclusion p38/caspase-3 mediated MEF2C pathway may involved in the injuries of hippocampal CA1 region of rats following ischemia/reperfusion.