Objective To study the effect of rhein on the process of tubular epithelial-mesenchymat transformation in kidney of diabetic rats. Methods Wistar male rats were randomly assigned to 3 groups: Control group (N group, n=12),diabetic group(D group, n=12), rhein treatment group(R group, n=12).The rats of rhein treatment group were treated with daily intragastric administration of periment. The excretion of urinary protein and serum creatine were measured. Histological changes of renal tissue were observed by HE and MASSON stain. Immunohistochemistry was performed to investigate the expression of E-cadherin, α-SMA,FN and TGF-β1 in kidney. Results Compared with the control group, the tubulointerstitial injury and the accumulation of extraeellular matrix protein in diabetic models were obvious(P＜0.01).Compared with the control group, the expression of E-cadherin was decreased significantly and the expression of α-SMA,FN and TGF-β1 was increased significantly in diabetic group. E-cadherin was negatively correlated with TGF-β1(rs=-0.60,P＜0.05),α-SMA and FN was positively correlated with TGF-β1(rs=0.88,P＜0.05;rs:0.91,P＜0.01).In comparison with diabetic group,rhein could up-regulate the expression of E-cad and down-regulate the expression of α-SMA and FN in renal tubular epithelial cells(P＜0.01).Conclusion Rhein could protect kidney by ameliorating interstitial fibrosis in diabetic rats. The mechanism may be depend on down-regulating the expression of TGF-β1 and suppressing tubular epithelial-mesenchymal transformation.