Abstract Objective Arginyl-fructosyl-glucose (AFG) is an early Maillard reaction product synthesized from arginine and maltose. Although antihyperglycemic activity of AFG has been reported several times in recent years, the amelioration effect of AFG on type 2 diabetes mellitus (T2DM) remains unclear. Method T2DM was induced in mice by high fat diet (HFD) and streptozotocin (STZ). Group 1 (n = 10, CON) and Group 2 (n = 80) were fed regular chow and HFD, respectively. After 4 weeks of HFD feeding, group 2 was injected with STZ at a dose of 100 mg/kg and the fasting blood glucose (FBG) level was tested for 4 weeks post-injection. Then, mice with FBG level above 7.8 mmol/L were divided into five equally-sized groups (n=10) and they were treated with vehicle, metformin, 50, 30 and 10 mg/kg of AFG for 4 weeks, respectively, and CON was treated with vehicle. Results Orally treatment with AFG resulted in the decrease of malondialdehyde, total cholesterol, total triglyceride, daily food intake and daily water intake and increase of body weight, superoxide dismutase and insulin. The histological examination and immunohistochemistry indicate that the hypoglycemic and insulin-sensitizing capability of AFG in diabetic mice were enhanced via improving the destruction of the pancreatic islets. Conclusion All of these results indicate the therapeutic effect of AFG on T2DM mice.