Aim To investigate the protective effects of fasudil hydrochloride on postconditioning of acute myocardial ischemia/reperfusion injury, and the potential mechanisms in rats. Methods Sixty rats were randomly divided into 5 groups: sham operation group, ischemia/reperfusion group, an inhibitor of PI3K group, fasudil hydrochloride group, fasudil hydrochloride and an inhibitor of PI3K group. There were 12 rats in each group. Animals were sacrificed after 180 minutes reperfusion to determine heart function parameters, plasma myocardial enzymes, cell apoptosis index and myocardial infarct size. Results The levels of apoptosis index and myocardial infarct size in the fasudil hydrochloride group were significantly lower than in the ischemia/reperfusion group （all P<0.01）. But using an inhibitor of PI3K, fasudil hydrochloride couldn’t protect myocardial ischemia/reperfusion injury, the levels of apoptosis index and myocardial infarct size in the fasudil hydrochloride and an inhibitor of PI3K group were significantly higher than in the fasudil hydrochloride group （all P<0.01）. Conclusion PI3K-Akt pathway was thought to be one of the main mechanisms responsible for the protection of fasudil hydrochloride postconditioning.