〔Abstract〕 Objective To investigate the respective effects of glibenclamide and metformin on antenatal and postpartum glucose metabolism for gestational diabetes mellitus(GDM) mice. Methods Streptozotocin was used to stimulate C57 BL/6 J mice to develop GDM. In addition to GDM control, treatment was respectively given with long-acting insulin, glibenclamide and metformin. The first day of pregnancy was defined as gestational day(GD0), body weight and fasting blood glucose were measured every 2 days from GD0. On GD18, 8 dams in each group were euthanized to collect livers. The remaining 8 dams in each group were housed for natural delivery. After 1 week of post-partum, glucose tolerance test(GTT) and insulin tolerance test(ITT) were measured for all mice. After 5 weeks of post-partum, the GTT and ITT were measured for all mice. The mice were then euthanized to collect livers. The hepatic levels of phosphor-protein kinase B(p-AKT), phosphor-Forkhead box transcription factor O1(p-FoxO1), glucose-6-phosphatase(G6 Pase), phosphoenolpyruvate carboxykinase(PEPCK) were measured respectively. Results Glibenclamide and metformin could decrease fasting blood glucose respectively in GDM mice with antenatal and 1 week postpartum(P<0.05). Compared with the GDM control, p-AKT and p-FoxO1 levels increased(P<0.05) while G6 Pase and PEPCK reduced(P<0.05) respectively in livers from the glibenclamide and metformin intervened groups. However,after 5 weeks of post-partum,the effects of two interventions on the GDM mice disappeared. Conclusions Glibenclamide and metformin may improve the glucose tolerance and insulin resistance for GDM mice with antenatal and 1 week postpartum,but have poor effects on those with 5 weeks postpartum.