Objective To investigate the mechanism of the pathogenesis of diabetic nephropathy (DN) by detecting the expressions of transforming growth factor (TGF)-β, Smad proteins andα-smooth muscle actin (α-SMA) in kidney biopsy of patients with diabetic nephropathy (DN). Methods Twenty-eight patients with DN who underwent renal biopsy were col-lected as DN group. Ten subjects without DN who underwent nephrectomy were taken as control group. The expressions of TGF-β1, TGF-βRⅠ,TGF-βRⅡ,Smad2/3 andα-SMA in renal tissues were detected by immunohistochemistry stain. Results (1)TGF-β1,TGF-β RⅠ,TGF-β RⅡ,and Smad2/3 were expressed in the glomeruli and tubules of both DN group and control group, while the expressions of TGF-βand Smad proteins were significantly higher in DN group than those in control group. At the early stage of DN, TGF-βand Smad proteins were significantly expressed even though there was no remarkable lesions observed by light microscopy. There was no correlation between increased expression and the progres-sion of DN. These proteins were not expressed after glomerulus and renal tubule fibrosis. (2) In control group,α-SMA was identified only in the vascular walls, glomerulus and renal tubules, while it was expressed in almost all parts of kidney in DN group. Conclusion TGF-β and Smad signals involved in the pathogenesis of DN, which may have similar pathogenesis with immune complex glomerulonephritis.