Objective To investigate the effect of morphine postconditioning on myocardial ischemiarepedusion(I/R)injury and the role of PI3K/Akt signaling pathway in the effect.Methods Seventy male SD rats weighing 280-330 g aged 16-17 weeks Were randomly divided into 5 groups(n=14 each):group Ⅰ sham operation(S);group Ⅱ I/R;group Ⅲ morphine postconditioning(M);group Ⅳ morphine postconditioning+ wortmannin(W+M);groupV wortmannin(W).Myocardial I/R injury wa.g produced by occlusion of anterior descending branch of left coronary artery for 45 min followed by 120 min reperfusion.In group M and W+M (groupⅢ,Ⅳ)morphine 1.25 mCkg was given iv at 3 min before and 2 min after reperfusion.In group W+M and W(groupⅣ,Ⅴ)wortmannin(a specific PDK inhibitor)15μ/gkg Was given iv at 20 min before ischemia. The animals were sacrificed at the end of 120 min repedusion for assessment of ischemic and infarct area and determination of total and phosphorylated Akt expression in myocardium by Western blot.Results There were no significant differences in the size of ischemic area and total Akt expression among the 5 groups. The infarct area was significantly smaller in group M than in group I/R. The were no significant differenees in the size of infarct area between group 1/R, W + M and W (group Ⅱ , Ⅳ,Ⅴ ). The phosphorylated Akt expression was significantly upregulated in group I/R and M as compared with group S, and was significantly higher in group M than in group I/R.Conclusion The PI3K/Akt signaling pathway activation is involved in the protective effect of morphine posteondifioning on myocardium against I/R injury.