Objectives: The purpose of this study was to investigate the effects of Polygoni Multiflori Radix Water Extract (PM) on the production of inflammatory mediators in RAW 264.7 mouse macrophages induced by lipopolysaccharide (LPS). Method : We examined effect of PM Extract on the cell viability of RAW 264.7 cells. Futhermore, we investigated anti-inflammatory effect of PM Extract by the production of proinflammatory cytokines such as NO, intracellular calcium, interleukin(IL)-1α, IL-3, IL-1β, IL-6, interferon inducible protein-10(IP-10), keratinocyte-derived chemokine(KC) and vascular endothelial growth factor(VEGF). Result : No significant changes have been found in the mouse macrophge cell viability by the PM Extract at the concentration of 25, 50, 100 and 200㎍/mL. The water extract of PM significantly inhibited the production of NO and intracellular calcium in the LPS-induced macrophages at the concentration of 25, 50, 100 and 200㎍ /mL. The water extract of PM significantly inhibited the production of IL-1α, IL-β, IL-3, IP-10, KC, VEGF in the LPS-induced macrophages at the concentration of 50, 100, and 200㎍/mL; IL-6 at the concentration of 100 and 200 ㎍/mL ; and IL-17 at 200㎍/mL. Conclusion : The water extract of PM significantly inhibited the production of NO, intracellular calcium, IL-1α, IL-3, IL-β, IP-10, KC, VEGF at the concentration of 50 ㎍/mL or higher in the LPS-induced macrophages with no changes in the cell viability of them. These results suggest that water extract of Polygoni Multiflori Radix has anti-inflammatory effect regulating the production of proinflammatory cytokines in the LPS-induced macrophages.