Objective: To observe the effect of Icariin on diabetic myocardial hypertrophy and explore its molecular mechanism. Methods: C57BL/6 mice were randomly divided into Ctrl group (normal control group), DM group (STZ intraperitoneal injection model), and DM+ICA group (diabetic C57BL/6 mice by intragastric Icariin solution 80mg/kg/d, for 3 consecutive weeks). Real-time quantitative PCR was used to detect myocardial hypertrophy markers BNP and β-MHC. Western blotting was used to detect myocardial AMPK, p-AMPK, mTOR, p-mTOR, LC3B and Beclin1 protein expression. Echocardiogram was used to detect left ventricular mass and ejection fraction. Results: Compared with the normal control group, the expression of myocardial hypertrophy markers BNP and β-MHC mRNA in diabetic mice were significantly increased; the expression of phosphorylated AMPK protein, autophagy-related protein LC3B and Beclin1 were significantly increased, and the expression of phosphorylated mTOR protein is significantly reduced; the left ventricular mass is significantly increased. The above changes can be reversed after treatment with Icariin, but the effect of Icariin is blocked by the autophagy inhibitor rapamycin. Conclusion: Icariin may inhibit autophagy and reduce diabetic myocardial hypertrophy through AMPK-mTOR signaling pathway.