Abstract: Objective: To observe the effect of probucol(PB) on the expression of transforming growth factor-1 and hemeoxygenase-1 (HO-1) in the renal tissue of diabetic nephropathy (DN) rats，and investigate the mechanism of PB in delaying renal interstitial fibrosis. Methods: Fifty male Sprague-Dawlay(SD) rats were randomly divided into experimental group and control group. The rats in the experimental group were given high-sugar，high-fat diet and intraperitoneal injection of streptozotocin to establish DN rat models, the model rats were then randomly divided into DN group and PB group. The rats in the PB group were treated by oral gavage of PB 500 mgkg-1d-1 . At the end of the experiment, the rats were weighed and the 24 h urinary protein and urinary N-acetyl--Dglucosaminidase(NAG) were checked, the rats were killed to collect the blood; and the serum biochemical parameters were observed, the kidney of the model rats was removed and performed tissue section to observe the renal interstitial fibrosis, the expression of renal tissue HO-1 and TGF-1 was detected by immunohistochemistry，the nucleic acid expression of the renal tissue TGF-1 and HO-1 was detected by rT-PCr. results: PB could relieve the proteinuria in the rats with DN，degrade the urinary NAG level, improve the serum total cholesterol, and reduce the serum creatinine and blood urea nitrogen level. It could also upgrade the level of HO-1mrNA kidney tissue and downgrade the level of TGF-1mrNA. Conclusions: PB can delay renal fibrosis, the mechanism of which may be that PB could up-regulate the expression of HO-1 and down-regulate the expression of TGF-1 .