Abstract: OBJECTIVE To investigate the changes of mTOR signaling pathways under the intervention of semaglutide. METHODS The type 2 diabetes rat model was established by an injection ofstreptozocin after five-week of high fat diet. The rats were divided into control group, 2 weeks model group, 4 weeks model group, and semaglutide group. Fasting blood glucose, total cholesterol, triglyceride, high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C) and fasting insulin levels were tested after the model established. M-mode echocardiography was performed for echocardiographic measurements. The alteration of mTOR, p-mTOR, S6K1, Atg5 and P62 inmyocardium was determined by Western blotting. RESULTS Compared with control group, the level of total cholesterol, triglyceride and LDL-C significantly increased in 2 weeks and 4 weeks model group, while HDL-C were significantly reduced. The level of fasting blood glucose was normal in the semaglutide group, and the levels of HDL-C increased (P<0.05) while the level of LDL-C decreased significantly(P<0.01). The expression of mTOR, p-mTOR and S6K1 were continuously increased in 2 weeks and 4 weeks model group compared with control (p<0.01), and SEM intervention group declined showed by western blotting. The expression of Atg5 and p62 were also increased consistently in model group with the duration of the development in diatetic rats, while the semaglutide group showed the decreased tread. CONCLUSION In the early stages of the development of diabetic cardiomyopathy, the intervention of semaglutide may suppress the expression of mTOR signaling pathways and eventually decrease the occurrence of autophagy in myocardial cells.