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BACKGROUND: Studies have confirmed that enalapril can alleviate myocardial injury caused by limb ischemia-reperfusion, but the mechanism of its action has not been reported. OBJECTIVE: To investigate the effect mechanism of enalapril reduction of myocardial injury by ischemia-reperfusion in the rat limb. METHODS: Forty-eight healthy adult male Sprague-Dawley rats were randomly divided into control group, model group, enalapril group and inhibitor group. Except for the normal control group, rats were bundled around the ligation of the posterior limbs with a rubber band for 3 hours, followed by 3-hour reperfusion to establish the model of limb ischemia-reperfusion. Intravenous injection of 0.3 mg/kg LY294002 was given in the inhibitor group 30 minutes before reperfusion. Enalapril group and inhibitor group were given intravenous infusion of enalapril 13 μg/kg/h immediately after reperfusion until the end of reperfusion. An equal amount of normal saline solution was given in the other two groups immediately after reperfusion. After 3 hours of reperfusion, the rats were killed and the myocardial tissue was taken. Myocardial histopathological changes, apoptotic index, apoptosis gene expression and cell conduction pathway protein expression were detected. The study was approved by the Laboratory Animal Ethical Committee of Shenyang Medical College in October 2019 with an approval No. (2019)85. RESULTS AND CONCLUSION: Compared with the model group, myocardial histopathological injury was reduced in the enalapril group. Compared with the enalapril group, myocardial histopathological injury was aggravated in the inhibitor group. Compared with the model group, myocardial apoptosis index (AI) was decreased, Bax expression was downregulated, PI3K, p-Akt and Bcl-2 expression was up-regulated in the enalapril group (P < 0.05). Compared with the enalapril group, myocardial apoptosis index was increased, Bax expression was up-regulated, PI3K, p-Akt and Bcl-2 expression was downregulated in the inhibitor group (P < 0.05). The mechanism by which enalapril reduces limb ischemia-reperfusion caused myocardial injury is related to activating PI3K/Akt signaling pathway and inhibiting cell apoptosis in rats. [ABSTRACT FROM AUTHOR]