Abstarct − As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we evaluated the effects of the methanol extract of Polytrichum commune Hedw (PCM) (Polytrichaceae) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E 2 (PGE 2 ) and pro-inflammatory cytokines release in murine macrophage cell line RAW 264.7. PCM potently inhibits the production of NO, PGE 2 , tumor necrosis factor (TNF)-α and interleukin (IL)-6. Consistent with these results, PCM also concentration-dependently inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-α and IL-6 at the mRNA levels without an appreciable cytotoxic effect on RAW 264.7 macrophage cells. Furthermore, PCM inhibited LPS-induced nuclear factor-kappa B (NF-κB) activation as determined by NF-κB reporter gene assay, and this inhibition was associated with a decrease in the nuclear translocation of p65 and p50 NF-κB. Taken together, these results suggest that PCM may play an anti-inflammatory role in LPS-stimulated RAW 264.7 macrophages through the inhibitory regulation of iNOS, COX-2, TNF-α and IL-6 via NF-κB inactivation.