〔Abstract〕 Objective To evaluate the effects of long-term exposure to high altitude hypoxia(HAH) on cardiac function in rats, and to explore whether the mechanism is related to autophagy in the process of myocardial fibrosis mediated by AMPK pathway. Methods Fifty male SD rats were housed at an altitude of 4 500 m. Ten rats were randomly selected for body weight, blood pressure, echocardiography, cardiac histology and autophagy protein examination at baseline, 1 week, 2 weeks, 4 weeks and 8 weeks. Thirty rats were randomly divided into two groups with 15 animals in each group, including control group and rapamycin group. Rapamycin group was administered by intraperitoneal injection [1 mg/(kg·d)]. The control group was intraperitoneally injected with the same volume of normal saline. The above examinations were carried out before the test and at the end of the 8 th week. Results Body weight, blood pressure and echocardiography showed that the systolic blood pressure, body weight, right ventricular end diastolic diameter(RVEDd) and left ventricular ejection fraction(LVEF) of rats exposed to HAH environment increased, while the pulmonary artery acceleration time(PAAT) decreased. Rapamycin reversed these changes. Histological analysis showed that the rats exposed to HAH environment had myocardial degeneration, necrosis and fibrosis, accompanied by monocyte infiltration, and increased myocardial fibrosis. Rapamycin reduced these changes. Western blot analysis showed that the Beclin-1, LC3-Ⅱ/Ⅰ and AMPK protein increased significantly up to 4 weeks, but were impaired after 8 weeks of HAH treatment in heart tissue. Rapamycin increased autophagy related markers Beclin-1, LC3-Ⅱ/Ⅰ and AMPK protein expression. Conclusion Long term exposure to HAH may damage cardiac function in rats, and its mechanism is related to autophagy in the process of myocardial fibrosis mediated by AMPK pathway.