Abstract: To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg·kg^-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen Ⅲ in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.