Abstract: AIM:To investigate the effect of irisin on the metabolism of glucose in type 2 diabetic mice (T2DM) and its mechanism. METHODS: T2DM was induced by a high-fat diet (HD) plus low-dose streptozotocin (STZ) intraperitoneal injection. Blood irisin was determined after irisin intraperitoneal injection by Western blot evaluation. Blood glucose was determined at 30, 60, 90, 120, 150, 180 and 210 min in T2DM+irisin group, respectively, by glucometer detection. The expressions of G6Pase and PEPCK were evaluated by Western blot. RESULTS: 1) Blood glucose increased 6 weeks after high-fat diet and glucose tolerance (IPGTT) decreased significantly in the diabetic mice. 2) Compared with control group, injections of irisin group plasma levels increased significantly (P<0.01). 3) Compared with T2DM group, in the group of intra-articular injections of normal saline, the level of blood glucose decreased 30 min after irisin ejection and reached its lowest level 120 min after irisin ejection (P<0.05). The level of blood glucose was close to the basal level 210 min after irisin injection. 4) G6pase and PEPCK expressions increased in diabetic mice. Irisin decreased G6pase and PEPCK expressions in diabetic mice (P<0.01). CONCLUSION: Irisin reduces instantaneous blood glucose level in type 2 diabetes mice possibly through decreasing hepatic gluconeogenesis.