Abstract: OBJECTIVE To investigate the effect of the union of Yiqi bushen fang and tripterygium wilfordii polyglycosidium(TWP) on expression of VEGF and inflammatory cytokines in rats with diabetic nephropathy(DN). METHODS To establish an experimental DN rat model through a high-fat diet. Unilateral nephrectomy and injection of streptozocin(STZ) through peritoneal cavity. animals were respectively administrated with irbesartan(15.75 mg·kg^-1·d^-1), TWP(3.15 mg·kg^-1·d^-1), Yiqibu shen fang(contained 21.42 g·kg^-1·d^-1 dried medicinal herbs) and the mixture of TWP and Yiqi bushen fang from 9th week to 16th week. At the end of 16th week, the level of IL-6 and TNF-α in serum was determined by ELIAS; the level of GLU in serum were determined by glucometer; the functions of kidney and urine protein creatinine ratio (P/C) were measured with Automatic Analyzer; the expression of VEGF in renal cortex were determined with methods of RT-PCR and immunohistochemical. The pathological changes of kidney were detected with light microscope and electron microscope. RESULTS Compared with normal rats, the level of Cr, BUN, GLU in serum and urine protein of DN rats increased significantly(P<0.05); the protein and mRAN expression of VEGF in renal cortex were also increased significantly(P<0.01); the level of IL-6 and TNF-α in serum were increased significantly(P<0.05); the pathologic change showed the number of podocyte decreased, foot processes broadening and integrating, mesangial area broadening, basement membrane thickening. After the treatment, the level of Cr, BUN and P/C were decreased significantly(P<0.05); the serum level of IL-6 and TNF-α were decreased significantly(P<0.05); accompanied with the down expression of VEGF(P<0.01), and pathological changes improved, especially in union of Yiqi bushen fang and TWP treantment group. CONCLUSION The joint of Yiqi bushen fang and TWP has protection effects on early renal injury in rats with DN, and the treatment mechanism might associated with the down adjustment of the renal expression of VEGF, and inhibition of IL-6 and TNF-α secretion.