Abstract: AIM To evaluate the effect of aerobic interval training(AIT) on myocardial ischemia reperfusion(MI/R) injury in high-fat diet-induced obese mice and the related mechanism. METHODS Sixty 2-month-old C57 mice were randomly divided into three groupscontrol mice with normal diet(Con), high-fat diet(HF) and high-fat diet mice with AIT(HF+AIT). Twelve weeks after feeding, mice were subjected to acute myocardial ischemia reperfusion(ischemia 30 min/reperfusion 4 h). Cardiac function was determined by echocardiography and related signal protein expression was detected by Western blot. RESULTS Twelve-week high-fat feeding led to obesity in mice and their weight significantly increased compared to control mice. AIT training effectively reduced the weight of HF mice and increased heart weight/tibia length ratio. Compared with control group, MI/R injury in HF obese mice significantly increased. AIT training effectively reduced MI/R injury in HF mice as evidenced by reduced infarct area and serum LDH level(P<0.05). AIT training also significantly improved myocardial functional recovery after MI/R, effectively improved left ventricular ejection fraction(EF) and decreased left ventricular short axis ratio(FS). Compared with HF group, AIT significantly enhanced the myocardial mitochondria SIRT3 and MnSOD expression in HF mice and reduced MI/R myocardial tissue oxidative stress in HF mice(P<0.05). CONCLUSION AIT effectively improves myocardial mitochondria SIRT3 and MnSOD in HF obese mice and increases mitochondrial antioxidant enzyme activity, thus reducing the obese mice MI/R injury and promoting heart function recovery after ischemia.