Objective: To evaluate the antidiabetic effect of Callicarpa nudiflora extract in streptozotocininduced diabetic rats. Methods: The chemical constituents in Callicarpa nudiflora extract were identified by UPLCQ- TOF-MS. Callicarpa nudiflora extract (0.15 and 0.3 g/kg) was orally administered to streptozotocin-induced diabetic rats for 42 d. The effects of Callicarpa nudiflora extract on body weight, blood glucose, serum insulin, total cholesterol, triglyceride, LDL-C and HDL-C were investigated, and its effect on liver and pancreatic pathology was assessed by histopathological analysis. Moreover, the expression levels of adenosine 5’-monophosphate-activated protein kinase (AMPK), glucose transporter type 4 (GLUT4), phospho-AMPK/AMPK, and p-acetylcoA carboxylase (P-ACC)/ACC in the skeletal muscles and liver were determined by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Results: A total of 34 compounds, including 8 iridoids, 14 phenylpropanoids, and 12 flavonoids, were identified from Callicarpa nudiflora extract. Callicarpa nudiflora extract significantly reduced blood glucose and significantly restored all other biochemical parameters to near normal levels, including serum insulin, total cholesterol, triglyceride, LDL-C, and HDL-C. Callicarpa nudiflora extract improved insulin resistance and reversed the damage in the liver and pancreas caused by diabetes. Furthermore, Callicarpa nudiflora extract increased the expression levels of phospho-AMPK, GLUT4, P-ACC, and insulin receptor substrate-1 and decreased the expression level of PPAR-gamma in diabetic rats. Conclusions: Callicarpa nudiflora extract improved oral glucose tolerance, lipid metabolism, insulin resistance, and reversed the diabetes-related damage in the liver and pancreas by activating the AMPK-ACC pathway.