Effect of Oenanthe javanica ethanol extract (OJE) on nuclear factor-${kappa}B$ (NF-${kappa}B$)-mediated inflammatory reaction in RAW 264.7 macrophage cells was investigated. The OJE dose-dependently inhibited secretions of tumor necrosis factor-${alpha}$ (TNF-${alpha}$) and prostaglandins $E_2;(PGE_2)$ from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and blocked LPS-induced expression of cyclooxygenase-2. To clarify mechanistic basis for its inhibitions of NF-${kappa}B$ and activator protein-1 (AP-1) activations, effects of OJE on activations of NF-${kappa}B$ and AP-1 genes by luciferase reporter activity were examined. The LPS-stimulated activations of NF-${kappa}B$ and AP-1 were significantly blocked by 400 and $600;{mu$}g/mL of OJE, implicating that OJE might regulate gene expression through more than one signaling pathway. Cytosolic degradation of I-${kappa}B{alpha}$ was inhibited by OJE dose-dependently, indicating that the nuclear translocation of p65 was inhibited by OJE. These findings suggest that the inhibition of LPS-stimulated COX-2 expression by OJE is due to its inhibition of NF-${kappa}B$ activation by blocking I-${kappa}B{alpha}$ degradation, which may be mechanistic basis of anti-inflammatory effects of OJE.