We evaluated the effects of extracts of Tsunokaori tangor peel on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2;(PGE_2)$ in RAW 264.7 cells. The ethyl acetate fraction of Tsunokaori tangor peel (EA-TTP) markedly inhibited the production of NO and $PGE_2$ in LPS-stimulated RAW 264.7 cells. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were down-regulated in a dose-dependent manner. Additionally, EA-TTP decreased the expression iNOS mRNA but not COX-2 mRNA. To determine the upstream signaling mechanism for the down-regulation of LPS-induced iNOS expression, we investigated the effect of EA-TTP on the degradation and re-synthesis of $I{kappa}B{alpha}$. EA-TTP dose-dependently delayed $I{kappa}B{alpha}$ degradation and increased $I{kappa}B{alpha}$ re-appearance following degradation, suggesting this as the mechanism by which EA-TTP suppressed iNOS gene expression. The EA-TTP also dose-dependently reduced the expression of the cellular stress-response protein heme oxygenase-1, and inhibited the LPS-induced sustained activation of extracellar signal-regulated kinase (ERK).