OBJECTIVE: To study the effects and the possible mechanism of Tangshenling (TSL) combined with telmisartan on early diabetic nephropathy (DN). Methods Eighty-one patients with early DN were randomly assigned into the control group (n=40) treated by telmisartan alone and the treated group (n=41) treated by TSL combined with telmisartan, and the conventional western therapy was given to all patients in both groups. Changes before and after treatment in symptoms and levels of urine albumin excretion rate (UAER), urine transforming growth factor beta1 (TGF-beta1), retinol binding protein (RBP) and beta2-microglobulin (beta2-MG), fasting blood glucose (FBG), serum creatinine (SCr), blood lipids, plasma atrial natriuretic peptide (ANP), serum collagen type IV (Col-IV) and TGF-beta1 were observed. RESULTS: Before treatment, no significant difference was shown in all these indexes between the treated group and the control group. After 8 weeks of treatment, the effective rates in symptoms improvement were higher in the treated group than those in the control group (P < 0.05 or P < 0.01); UAER, urine RBP, beta2-MG and TGF-beta1, serum TC, TG, Col-IV and TGF-beta1, and blood pressure were significantly lowered in both groups after treatment (P < 0.05 or P < 0.01); and the treated group showed a better effect than the control group in improving all the above-mentioned indexes except the blood pressure (P < 0.05); but there was no significant difference in the changes of FBG, SCr and blood pressure between the 2 groups (P > 0.05); after treatment, plasma ANP significantly lowered in the treated group (P < 0.01), while there was no significant change of that in the control group (P > 0.05). Conclusion Combination of TSL and telmisartan has a better effect than telmisartan on DN in early stage. Its mechanism might be related to the decrease of ANP and TGF-beta1 and improvement of lipids metabolism and renal tubular interstitial pathological changes.