Abstract: AIM To investigate the role of mTOR-mediated autophagy in melatonin-alleviated myocardial ischemia reperfusion injury. METHODSMale C57BL/6 mice were randomly divided into four groups: sham (Sham) group, melatonin group ［10 mg/(kg·d)］ control (Mel) group, ischemia reperfusion (I/R) group and ischemia reperfusion plus melatonin ［10 mg/(kg·d)］ (Mel+I/R) group. Coronary artery left anterior descending artery ligation was used to prepare myocardial ischemia for 30 min and reperfusion for 4 h. The pathological morphological changes in the myocardial fiber were analyzed by HE staining. Lactate dehydrogenase content in serum was determined and myocardial cell apoptosis was tested with TUNEL method. The expressions of LC3I/II, Beclin1 and phosphorylation of mTOR were detected using Western blot and the expression of LC3B was detected using immunofluorescence staining. RESULTSNo significant differences were found in the parameters detected between Sham and Mel. I/R significantly increased the content of LDH (P<0.01), accompanied by the disordered arrangement of myocardial fibers, up-regulation of LC3II and Beclin1, increased myocardial apoptosis index, and down-regulation of p-mTOR (P<0.01). Immunofluorescence staining showed significantly increased expression of LC3B (P<0.01). These effects were significantly attenuated by melatonin (P<0.01). CONCLUSIONMelatonin can significantly reduce myocardial ischemia reperfusion injury by regulating mTOR-mediated autophagy.