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Objective: To observe the effects of Zhenqing Recipe (ZQR) on transforming growth factor-β1 (TGF-β1) in diabetic nephropathy (DN) with hypertension rats and investigate its mechanisms.Methods: DN with hypertension models were made by 4 weeks high-salt diet with high sugar and fat for male Wistar rats, and intraperitoneal injection of streptozotocin (STZ).The model rats were randomly divided into three groups: untreated model group (n=l 5); metformin group (n=1 5), orally given metformin; ZQR group (n=1 5), orally administrated ZQR, for 8 weeks respectively.Blood pressure was measured before modeling and after treatment of 2, 4, 8 weeks.Fasting blood glucose (FBG), total triglyceride (TG) and total cholesterol (TC) and urine albumin excretion (UAE) of rats were observed and recorded.Renal histomorphology with PAS staining was observed by the light microscope.TGF-β1 in was detected by immunohistochemical assay and TGF-β1 mRNA in renal cortex was detected by RT-PCR.Results: The base blood pressure of rats has no significant difference before modeling (P>0.05).After 4 weeks of treatment, compared with model group, blood pressure in metformin group decreased (P<0.01), blood pressure in ZQR group was slightly lower (P<0.05).When 8 weeks, the rebound of blood pressure in metformin group is appropriate with the model, the blood pressure of ZQR reduced significantly (P<0.01).Compared with model group, FBG,UAE and TG in ZQR groupand metformin group significantly decreased (P<0.01), TC levels also decreased (P<0.05).The level of TGF-β1 in ZQR group and the metformin group decreased (P<0.01), and level of TGF-β1 in ZQR group was lower significantly than that in metformin group (P<0.05).The mRNA expressions of TGF-β1 in ZQR group and the metformin group were significantly lower than model group (P<0.01).Pathological changes were ameliorated in ZQR and metformin group compared with model group.Conclusion: ZQR can regulate blood pressure and improve renal functional morphology through down-regulation of TGF-β1 and its mRNA expression in DN with hypertension rats.We initially proved that the inhibition effect of TGF-β1 in ZQR is better than metformin, and ZQR can lower blood pressure to normal levels with a better step-down smoothly and a long-term efficacy.