Tumor necrosis factor- (TNF) and nuclear factor kappaB (NFB) play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic stellate cells curcumin, a polyphenolic compound, is shown to antagonize TNF elicited NFB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared to enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin treated (curcumin), and enalapril treated (enalapril) groups. Sham operated animals served as control. Renal dysfunction in the Nx group, as evidenced by elevated BUN, plasma creatinine, proteinuria, segmental sclerosis and tubular dilatation was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared to the control, the Nx had significantly higher plasma and kidney TNF which was associated with NFB activation in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor (PPAR) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF. Curcumin dose dependently antagonized TNF mediated decrease in PPAR and blocked transactivation of NFB and repression of PPAR, indicating that the antiinflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.