Although inflammation acts as host defense mechanism against infection or injury and is primarily a self limiting process, inadequate resolution of inflammatory responses leads to various chronic disorders. This work aimed to elucidate the anti-inflammatory effects of 2-methoxy-4-vinylphenol (2M4VP) isolated from pine needles in LPS-stimulated RAW264.7 cells. Some key pro-inflammatory mediators including nitric oxide (NO), prostaglandins ($PGE_2$), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied by sandwich ELISA and western blot. In addition, suppression of NF-${kappa}B$ and MAPK activation, and histone acetylation was studied by western blot analysis and immunostaining. 2M4VP dose-dependently inhibited NO and $PGE_2$ production and also blocked LPS-induced iNOS and COX-2 expression. In addition, 2M4VP potently inhibited the translocation of NF-${kappa}B$ p65 into the nucleus by $I{kappa}B$ degradation following $I{kappa}B-{alpha}$ phosphorylation and the phosphorylation of MAPKs such as p38, ERK1/2, and JNK. Also, 2M4VP inhibited hyper-acetylation of histone H3 (Lys9/Lys14) induced by LPS. Taken together, our results suggest that 2M4VP, a naturally occurring phenolic compound, exert potent anti-inflammatory effects by inhibiting LPS-induced NO, $PGE_2$, iNOS, and COX-2 in RAW264.7 cells. These effects are mediated by suppression of NF-${kappa}B$ and MAPK activation and histone acetylation.