AIM To investigate the mechanisms of angiotensin Ⅱ receptor antagonist irbesartan (Irb) on the expression of connective tissue growth factor(CTGF) in streptozotocin (STZ) induced diabetic rats. METHODS SD rats were randomly divided into three groups: normal control (group N, n =7), diabetic nephropathy (group DN, n =6) and diabetic nephropathy treated with Irb (group DNI, n =7). Diabetes was induced by injection of STZ intraperitoneally. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), 24 hour proteinuria (24hUpro) were observed in the rats at week 4, 8, 12 respectively. Creatinine clearance (Ccr) was determined at week 12 when the rats were sacrificed. Renal expression of CTGF and transforming growth factor β 1 (TGF β 1) were determined by immunohistochemistry. The extent of glomerulosclerosis(GS) was measured by CMIAS color image system. RESULTS 24hUalb? 24hUpro? Ccr? renal expression of CTGF and TGF β 1 were significantly increased in DN group compared with that in N group( P< 0.01 respectively). Irb treatment significantly prevented the increasing of Ualb excretion, 24hUpro, Ccr in diabetic rats ( P< 0.01 respectively). Furthermore, Irb markedly inhibited the increasing of glomerulosclerosis( P< 0.01). We demonstrated that Irb significantly prevented the immunostaining of CTGF and TGF β 1 ( P< 0.01 , P< 0.05 respectively). In addition, the extent of CTGF expression is positively correlated with the glomerular immunostaining of TGF β 1 ( P< 0.05). CONCLUSION Irb exerted renal protective effect on diabetic rats and inhibited the expression of CTGF.