【Abstract】 Objective: To study the role of PI3K-Akt pathway in the attenuation of ischemia-reperfusion (IR) injury conferred by diazoxide (DZ) postconditioning in rat myocardium. Methods The in vivo rat myocardial IR injury model was used. 55 adult male SD rats were randomly divided into group A (sham operation ), group B (ischemia-reperfusion ), group C (DZ postconditioning), group D (wortmannin, WTN) and group E (DZ postconditioning + WTN). Hemodynamic parameters were monitored continuously, and myocardial infarct size and plasma CK levels were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and Colorimetric measurement respectively, and the pathological changes were examined in myocardial tissue by HE staining as well. Results Compared with the group B, cardiac function significantly were improved (P＜0.01), and myocardial infarct size and plasma CK levels were significantly lower, and the myocardial injury were also less in group C and E (P＜0.01); while cardiac function were improved significantly and the myocardial infarct size and plasma CK levels of group C were significantly lower than group E (P＜0.05); and the tissue damage was even less as well. There was no difference between group B and D（P＞0.05）. Conclusion Cardioprotection induced by diazoxide (Diazoxide, DZ) postconditioning partly dependents on the activation of PI3K-Akt pathway.