Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and expansion of glomerulus cavities inGroupsB,C,D andE were observed.However, damage degree inGroups C,D andE were more moderate than that inGroupB.Conclusions:Pioglitazone can reduce kidney damage in diabetic rats, which may be attributed to its role in increasing glomerularPCX protein expression and inhibiting urinary excretion ofPCX, and its effect is dose dependent.