The inhibitory effect of luteolin on cyclooxygenase (COX)-2 expression was investigated in 12-O-tetradecanoyl phorbol-13-acetate (TPA), a prototype tumor promoter, activated human lung epithelial A549 cells. Luteolin mitigated TPA-stimulated COX-2 expression in a dose-dependent manner without any cytotoxicity. Since nuclear factor (NF)-κB plays a critical role in inflammatory casdades, activated status of NF-κB was estimated through the phosphorylation of p65, one subunit of NF-κB by western blot analysis. Phosphorylation of p65 was dose-dependently inhibited by luteolin treatment. Mitogen-activated protein kinases (MAPKs) are also important signaling molecules for COX-2 regulation. Luteolin treatment inhibited TPA-induced extracellular-signal regulated protein kinase (ERK) phosphorylation that is crucially related to inflammatory cascades regulation. These results suggest that luteolin attenuates TPA-induced COX-2 expression by blocking NF-κB activation through suppressed ERK phosphorylation in A549 cells.