Abstract: Objective: To investigate whether the cardioprotection of ethanol postconditioning can be attenuated by inhibition of phosphatidylinositol-3 kinase(PI3K) pathway in isolated rat hearts subjected to ischemia and reperfusion. Methods: Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 minutes of regional ischemia(occlusion of left anterior descending artery) followed by 120 minutes of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. Results: In contrast to ischemia and reperfusion, ethanol postconditioning improved the recovery of left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure,rate pressure product and reduced LDH release during reperfusion(P < 0.01). Administration of PI3K inhibitor wortmannin attenuated the effect of ethanol postconditioning,the recovery of hemodynamic parameters were inhibited(P < 0.05-P < 0.01),LDH release was increased(P < 0.01). Conclusions: These findings indicate that inhibition of PI3K pathway can attenuate the cardioprotection of ethanol postconditioning.