OBJECTIVE： To study the preventive effect and mechanism of butylphthalide on myocardial ischemia-reperfusion injury in rats. METHODS： SD rats were randomly divided into sham operation group， model group， butylphthalide low-dose， medium-dose， high-dose groups （50， 75， 100 mg/lg）， 10 in each group. All rats were intragastrically administrated related drugs once a day， sham operation group and model group were intragastrically administrated equal amount of normal saline， for 3 d. After last administration， except for sham operation group， 120 min of repertusion was conducted. Ratio of myocardial infarction area， apoptosis rate of myocardial cells， expressions of apoptosis-related protein [proapoptotic proteins （Caspase-3， Fas， Caspase-9）， apoptotic protein （Bcl-2）]， left ventricular ejection fraction （LVEF）， and content of vascular endothelial growth factor （VEGF） in serum of rats in other groups were detected. RESULTS： Compared with sham operation group， myocardial infarction area and apoptosis rate of myocardial cells in model group were obviously increased； expressions of Caspase-3， Fas， Caspase-9 protein in myocardial cells were obviously enhanced， Bcl-2 protein expression was obviously weakened； LVEF and serum VEGF content were obviously reduced （P＜0.01）. Compared with model group， except that LVEF in butylphthalide low-dose group didn’t changed obviously （P＞0.05）， above indexes in other administration groups improved obviously （P＜0.05）. Compared with butylphthalide low-dose group， myocardial infarction area and apoptosis rate of myocardial cells in butylphthalide high-dose group were obviously decreased （P＜0.05）； expressions of Caspase-3， Fas， Caspase-9 protein in myocardial cells in butylphthalide medium-dose， high-dose groups were obviously weakened， and Bcl-2 protein expression was obviously enhanced （P＜0.05）. CONCLUSIONS： Butylphthalide can effectively reduce myocardial ischemia-reperfusion injury in rats， protect cardiac functions， and its mechanism may be related with up-regulating VEGF.