We examined the ability of the flavonoids quercetin and kaempferol to modulate inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reactive C-protein (CRP) expression, and to induce changes in the nuclear factor kappa B (NF-κB) pathway in the human hepatocyte-derived cell line Chang Liver. Cells were incubated with a cytokine mixture supplemented with quercetin or kaempferol (5 to 200 μmol/l). Kaempferol produced a significant concentration-dependent decrease of iNOS, COX-2 and CRP protein level at all concentrations, but the percentage of inhibition induced by quercetin was reduced at high concentrations. Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP. Inhibitory effects by quercetin and kaempferol were also observed on NF-κB activation and on protein concentration of the phosphorylated form of the inhibitor IκBα and of IKK (IκB kinase)α. The present study suggests that the modulation of iNOS, COX-2 and CRP by quercetin or kaempferol may contribute to the anti-inflammatory effects of these two structurally similar flavonoids in Chang Liver cells, via mechanisms likely to involve blockade of NF-κB activation and the resultant up-regulation of the pro-inflammatory genes. Our data also indicate that the minor structural differences between both compounds determine differences in their inhibitory capacity.