This study was to investigate the anti-inflammatory activity of ethanolic extract of Sargassum confusum (SCEE). LPS is recognized by TLR4 on the macrophage surface, which activates the NF-kappa B and MAPK signaling pathways, increasing the expression of inflammatory cytokine like interleukin-6 (IL-6), IL-1 beta, and tumor necrosis factor (TNF)-alpha and inflammatory mediators such as nitric oxide (NO) and cyclooxygenase-2 (COX-2). The anti-inflammatory effect of SCEE (0, 1, 10, 50 mu g/mL) was identified using LPS stimulated RAW 264.7 macrophages. As a result, it was confirmed that inflammatory factors were suppressed by inhibiting expression of COX-2 and iNOS without any cytotoxicity. In addition, phosphorylation of ERK, JNK and NF-kappa B p65, transcription factors, were inhibited by SCEE does-dependent manner. These results suggest that SCEE has an anti-inflammatory effect and can be used as a material for health functional foods to prevent inflammatory diseases.