Abstract： Objective:To investigate the effect of modified Taohong Siwu Decoction(桃红四物汤)on inflammatory factors and renal fibrosis in rats with diabetic nephropathy(DN)based on IKKβ/NF-κB/COX-2 signaling pathway.Methods:Ten rats were randomly selected as normal control group,and the remaining rats were established as DN models by feeding high-fat diet combined with intraperitoneal injection of strepto-zotocin(35 mg/kg).After successful preparation,the modeled rats were divided into model control group,irbesartan group(0.0135 g/kg),and modified Taohong Siwu Decoction(3.24,6.48 and 12.96 g/kg).Rats in each group were given corresponding medicine by gavage for 16 weeks,and fasting blood glucose(FBG),24-hour urine protein quantification(24 hUTP),serum creatinine(Scr),and blood urea nitro-gen(BUN)were detected at the end of 16 weeks.The plasma expressions of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay(ELISA).The pathological changes in re-nal tissues were observed by HE staining and MASSON staining.Real-time polymerase chain reaction(Real-time PCR)was used to measure the mRNA expressions of iKαb kinase(Iκkβ),nuclear transcription factor-κb p65(Nfκb p65),cyclooxygenase-2(Cox2),transforming growth factor-β1(Tgfβ1),collagen Ⅳ(ColⅣ),and α-smooth muscle actin(α-sma).Immunohistochemistry(IHC)was employed to detect the protein expressions of TGF-β1,COL-Ⅳ,α-SMA and,NF-κB p65 in kidney tissue,and Western blotting was performed to determine the protein expressions of IKKβ,NF-κB p65 and COX-2 in kidney tissue.Results:Compared with the normal control group,the model control group had elevated FBG,24hUTP and BUN(P＜0.05).Light microscopy revealed glomerular hypertrophy,increased mesangial matrix,thick-ened basement membrane,narrowing of renal capsule and partial vacuolar degeneration of renal tubules in the model control group,and there was an increase in serum IL-1β,IL-6 and TNF-α(P＜0.05),the mRNA and protein expressions of Tgfβ1,ColⅣ,and α-sma(P＜0.05),and the mRNA and protein expressions of Iκkβ,Nfκb p65,and Cox2 in kidney tissue(P＜0.05).Compared with the model control group,modified Taohong Siwu Decoction(6.48 and 12.96 g/kg)reduced the 24 hUTP and BUN in DN rats,and down-regulated IL-1β,IL-6 and TNF-α(P＜0.05).They also alleviated the degree of pathological damage,and inhibited the mRNA and protein expressions of related factors in IKKβ/NF-κB/COX-2 signaling pathway as well as fibrosis-related factors(P＜0.05).Conclusion:Modified Taohong Siwu Decoction can decrease inflammatory response and fibrosis progression by inhibiting the IKKβ/NF-κB/COX-2 signaling pathway in DN rats,and relieve renal patho-logical damage,showing a clear renal protective effect.