To investigate the effects of Tripterygium wilfordii polyglycoside (TWP) on the expressions of nuclear factor kappa B (NF-κB), chemokine (C-C motif) ligand 5 (CCL5), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and other inflammatory factors in diabetic nephropathy (DN) rats.The diabetic model was induced by a single intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into three groups: normal control group, diabetic model group and TWP (1.8 g/kg.d) treatment group. Kidney index, blood glucose (BG), glycosylated hemoglobin (HbA1c), creatinine (Scr), blood urea nitrogen (BUN) and other biochemical criterions were measured after eight-week treatment. The concentration of high sensitive C-reactive protein (hs-CRP) in serum and IL-6, TNF-α, CCL5 in kidney homogenate were detected by ELISA. The pathological changes of kidney were observed by HE staining and the expression of NF-κB in kidney was tested by immunohistochemistry.Compared with the model group, TWP improved evidently the general situation of rats. The levels of BG, HbA1c, kidney index, Scr and BUN were reduced significantly (P<0.01) and the body mass was elevated significantly (P<0.01). Additionally, the content of hs-CRP in serum, the levels of IL-6, TNF-α, and CCL5 in kidney homogenate and the expression of NF-κB in kidney decreased obviously in TWP group compared with the model group(P<0.01). The pathological changes of kidney were also relieved by TWP treatment.TWP treatment could reduce the expressions of inflammation cytokines in serum and kidney and relieve the nephropathy in diabetic rats.