Objective:To observe the effect of metformin on urinary nephrin excretion in type 2 diabetic model rats and investigate its protection of glomerular podocytes. Methods: Type 2 diabetes SD rats induced by high fat diet/ streptozotocin (HFD-STZ) were randomly divided into 3 groups: the diabetic model group, the metformin group, the glibenclamide group,and the normal control group. Blood glucose (BG), urine albumin (UALB) and nephrin excretion were monitored before and after the intervention, and glycosylated hemoglobin (HbA1c) was measured at the end of the study. Results: (1)BG and HbA1c levels of diabetic rats were significantly higher than those of normal group (P < 0.05); BG and HbA1c levels of the metformin and glyburide group were significantly lower than those of the type 2 diabetic model group (P < 0.05) at the end of the 4th and 8th week, but there were no significant differences between the two intervention groups. (2)At the end of the 4th and 8th week, UACR in all diabetic rats was significantly higher than that of the normal group (P < 0.05), which was significantly decreased in the metformin and glyburide group when compared with the type 2 diabetic model group (P < 0.05). There were no significant differences between the two intervention groups (P > 0.05) at the 4th week, but statistically differences were found at the 8th weeks (P < 0.05). (3)There were no significant differences of UNER among the 4 groups at the end of the 0th and 2nd weekend. At the end of the 4th and 8th week, UNER in the diabetic groups was significantly higher than that of the normal group (P < 0.05). UNER was significantly decreased in the metformin and glyburide group compared with the diabetic model group. The level of UNER in the metformin group was obviously lower than that of the glyburide group (P < 0.05). (4)Pearson correlation analysis showed that UNER was positively correlated with UACR(r = 0.846, P < 0.05). Conclusion: Metformin can decrease the excretion of urinary nephrin and provide some protection for glomerular podocyte in diabetic rats, which is not completely dependent on its hypoglycemic effect.