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.