〔Abstract〕 Objective To observe the effects of metformin(MET) on the MIF,CD74 and podocalyxin(PCX) expression in renal tissues of type 2 diabetic mellitus(T2 DM) rats,and explore its possible renoprotective mechanisms. Methods 10 SD rats served as normal control group(NC,n=10), 30 type 2 diabetes SD rats induced by high fat diet and streptozotocin were randomly divided into DM group, MET group and glibenclamide(GLY) group. 8 weeks later, fasting blood glucose(FBG), hemoglobin A1 c(HbA1 c),blood urea nitrogen(BUN), urine albumin/creatinine(UACR), MIF/creatinine(UMCR), CD74/creatinine(UCCR), PCX/creatinine(UPCR), and MIF,CD74, PCX mRNA and relative protein expression in renal tissue were measured. Results (1) The FBG, HbA1 c, BUN, UACR, UMCR, UCCR, UPCR and the mRNA and protein expression of MIF and CD74 in renal tissue in MET group and GLY group were significantly lower than those in DM group,but higher than those in NC group(P<0.05). The expression of PCX in renal tissue was significantly higher than that in DM group, which was lower than that in NC group(P<0.05).(2) Compared with GLY group, UACR, UMCR, UCCR,UPCR and the expression of MIF and CD74 mRNA and protein in renal tissue in MET group decreased significantly, and the expression of PCX was significantly increased. There was no significant difference in FBG and HbA1 c levels between two groups. Conclusion MET exerts a reno-protective effect of type 2 diabetic rats, which may be related to its inhibition of the MIF-CD74 axis-mediated inflammatory cascade.