Objective: To investigate the effect of transforming growth factor-β1(TGF-β1) and connective tissue growth factor(CTGF)on the early stage of diabetic nephropathy. Methods: Murine diabetic models were induced with streptozotocin (STZ). Rats were randomized into normal control group (NC) and diabetes group (DM). The body mass weight was measured every week, and the level of blood glucose was measured every two weeks. The biochemical data and indicators related to the renal function were detected in rats sacrificed after 8 weeks of experiments. At the same time, the liquid nitrogen frozen specimens from renal cortex were taken to analyze levels of TGF-β1, and CTGF mRNA by the method of RT-PCR. The protein expression of TGF-β1 and CTGF were determined by immunohistochemistry. Results: Compared with NC group, levels of blood urea nitrogen (BUN), 24 h urinary volume and urinary microalbumin (UMA) and kidney hypertrophy index were significantly higher in DM group (P 0.01), but the serum creatinine was significantly decreased (P 0.01). Results of real time quantitative PCR showed that levels of TGF-β1 and CTGF mRNA expression were significantly higher in DM group than those of NC group. Conclusion: The levels of TGF-β1 and CTGF mRNA expression were significantly increased in the early stage of diabetic nephropathy, which has a very important role for evaluating the process of diabetic nephropathy.