Water Fermented and Ethanol Fermented Extracts from Rhei Radix et Rhizoma exhibit potent anti-inflammatory activity with an unknown mechanism. To elucidate the molecular mechanisms of W-FR and E-FR on pharmacological and biochemical actions in inflammation, we examined the effect of W-FR and E-FR on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether FR inhibited nitric oxide (NO), tumor necrosis factor-${alpha}$ (TNF-${alpha}$), interleukin-6 (IL-6) and the expressions of iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that FR inhibited LPS-induced NO, TNF-${alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that W-FR and E-FR have inhibitory effects on LPS-induced TNF-${alpha}$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage.