Fibroblast growth factor(FGF)-21 is a new member of the fibroblast growth family. Recent studies show that FGF-21 is a novel regulator for glycemic control in various type 2 DM models. However, its potential to treat type 1 diabetes mellitus has not been explored. An evaluation of the function and mechanism of FGF-21 was made in hepatic glucose metabolism of type 1 diabetes mouse model with slow-onset of the impaired glucose tolerance induced by STZ. The mice were administrated with FGF-21, the mRNA expression of GLUT1 and 4 in the liver were detected by the real-time PCR and glycogen synthesis was examined by the anthrone method. The results showed that FGF-21could lower the blood glucose level of the type 1 diabetes model in a dose-depend manner. The blood glucose level of the experimental animals maintained at normal level by injection of the FGF-21 once a day. For the first time, the synergistic effect of FGF-21 with insulin in the animal model was found. Unlike insulin that stimulated GLUT4 expression, FGF-21 could increase the mRNA expression of GLUT1, co-treatment (CT) with insulin and FGF-21 could increase the mRNA expression of both GLUT1 and 4. After long term treatment, the same as insulin, FGF-21 also stimulated glycogen synthesis of the model mice. The results suggested that FGF-21 can regulate glucose metabolism through GLUT1 expression, stimulate glycogen synthesis and improve glucose metabolism in type 1 diabetes model. Moreover, CT administration could increase both GLUT1 and 4 expressions. These data provide the first evidence for clinic application of FGF-21 for treatment of type 1 diabetes patients.