Objective: Diabetic nephropathy （DN） is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes microangiopathy is still poorly understood. The WNT pathway is activated in DN and regulating β-catenin protein levels is referred to as the canonical Wnt/β-catenin pathway. Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN

exogenous administration of angiotensin II receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN. The aim of the study was to determine the β-catenin expression and the possible protective effects of irbesartan

an angiotensin II type 1 receptor blocker （ARB） in a rat model of streptozotocin（STZ）-induced diabetic nephropathy. Methods: STZ-induced DN in rats was assessed biochemically by measuring urine volume

protein and creatinine clearance as well as Kidney weight/body weight （KW/BW） and the index of mesangial expansion. Three groups of male Sprague-dawley rats were used. The ?rst group consisted of non-diabetic control rats （control）. The second group was the untreated diabetic rats（STZ+vehicle）. The third group consisted of diabeti rats treated with irbesartan

50 mg/kg for 12 weeks （STZ+irbesartan）. Immunohistochemical stainings and real time PCR for β-catenin were performed in renal cortex of rat modals. Results: Marked hyperglycemia

polyuria

proteinuria

renal hypertrophy

mesangial matrix expansion and glomerular hyper?ltration were observed in STZ diabetic rats. The levels of microalbuminuria and KW/BW in the STZ+irbesartan group were lower than those in the STZ+vehicle group （P<0.05）. The up-regulated immunostaining and mRNA expression of β-catenin were decreased in renal cortic of the Irbesartan-treated diabetic group

but there was no significant difference compared to the untreated diabetic group. Conclusion: The data suggest that irbesartan ameliorates proteinuria and renal hypertrophy

charactered damages of STZ-induced early-stage DN in rats

but its effective drug target is not to inhibit the up-regulated expressions of β-catenin.