Inflammation is a host defense mechanism that is activated in response to harmful substances or pathogens. However, an excessive inflammatory response is a problem in itself. Macrophages secrete inflammatory mediators such as nitric oxide (NO) or cytokines through various pathways such as the nuclear factor kappa B (NF-${kappa}B$)-activated pathway after recognizing pathogen-like lipopolysaccharides (LPSs). In this study, anti-inflammatory effects of Eupatorium chinensis var. simplicifolium (EUC) extracts were investigated using LPS-stimulated RAW 264.7 macrophages. The EUC root extract significantly reduced NO production, inducible nitric oxide synthase (iNOS) expression, and cyclooxygenase-2 expression in a concentration-dependent manner. In addition, the EUC root extract reduced phosphorylation of mitogen-activated protein kinases and protein kinase B, which is upstream of NF-${kappa}B$. The EUC root extract also reduced the degradation of inhibitory kappa B. These results indicate that EUC root extract exerts anti-inflammatory effects, which are mediated by inhibition of iNOS expression and the NF-${kappa}B$ pathway.