Previous studies have characterized the total polyphenolic contents, antioxidant activity, tyrosinase, elastase, and NO production of halophytes. Halophytes are distributed among many countries; however, it has not been properly utilized. In this study, we investigated the inhibitory effect of halophyte Euphorbia helioscopia (E.H.) on the LPS-induced inflammatory response in RAW 264.7 macrophages by MTT assay, NO assay, ELISA, and western blot analysis. Our results demonstrate that E.H. reduced LPS-induced NO and PGE 2 in addition to pro-inflammatory mediators, IL-6, IL-1β and TNF-α. Furthermore, E.H. inhibited LPS-induced activation of NF-κB, via IκBα degradation and phosphorylation of JNK and ERK. Our data suggest that the E.H. anti-inflammatory effect is a result of inhibition of LPS-induced NO, PGE 2 , IL-6, IL-1β, and TNF-α production via downregulation of the NF-κB and MAPK pathway.