Objective To investigate the role of transforming growth factor-β1(TGF-β1)/Smad4 pathway in development of renal fibrosis in streptozotocin(STZ)-induced diabetic nephropathy(DN) rats and explore its possible mechanism.Methods Male Wistar rats weighing 180-220 g were divided into 5 groups:group A(normal control),group B [diabetes mellitus(DM) 2 weeks],group C(DM 4 weeks),group D(DM 8 weeks),and group E(DM 16 weeks).Except for the normal control group,other groups were induced DM by single injection of STZ(55 mg/kg) respectively.Blood glucose level,serum creatinine,and 24-hour urine protein were examined.Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique,Western blot,and real-time PCR.mRNA expressions of stromelysin-1(MMP-3),tissue inhibitor of metalloproteinase-1(TIMP-1),and collagen Ⅲ in kidney were also detected by real-time PCR..Results The levels of blood glucose,serum creatinine,and 24-hour urine protein in rats of group B,C,D,and E were higher than those of the control group.With the progression of renal fibrosis,the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated.In addition,the renal MMP-3 mRNA expression diminished in diabetic rats,while TIMP-1 and collagen Ⅲ mRNA increased.Conclusions In STZ-induced diabetic rats,the TGF-β1/Smad4 appears to play an important role in renal fibrosis of DN.The increased expression of TGF-β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1/Smad4 pathway,which contributes to the progression of renal fibrosis in diabetic rats. Objective To investigate the role of transforming growth factor-β1 (TGF-β1) / Smad4 pathway in development of renal fibrosis in streptozotocin (STZ) -induced diabetic nephropathy (DN) rats and explore its possible mechanism. Methods Male Wistar rats weighing 180- 220 g were divided into 5 groups: group A (normal control), group B [diabetes mellitus (DM) 2 weeks], group C (DM 4 weeks), group D (DM 8 weeks), and group E ) .Except for the normal control group, other groups were induced by DM by single injection of STZ (55 mg / kg) respectively. Blood glucose level, serum creatinine, and 24-hour urine protein were examined. Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique, Western blot, and real-time PCR. mRNA expressions of stromelysin-1 (MMP-3), tissue inhibitor of metalloproteinase-1 also detected by real-time PCR..Results The levels of blood glucose, serum creatinine, and 24-hour urine protein in rats of grou p B, C, D, and E were higher than those of the control group. The progression of renal fibrosis, the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated. In addition, the renal MMP- 3 mRNA expression diminished in diabetic rats, while TIMP-1 and collagen III mRNA increased. Confins In STZ-induced diabetic rats, the TGF-β1 / Smad4 appears to play an important role in renal fibrosis of DN. β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1 / Smad4 pathway, which contributes to the progression of renal fibrosis in diabetic rats.