The macrophages, known as major cells involved in inflammatory response, are activated by immune cell-producing cytokine as well as by several stimuli to produce proinflammatory cytokine, and nitric oxide (NO), prostaglandin E2 (PGE₂) with are related with inducinle NOS (iNOS) and cyclooxygenase-2 (COX-2). In this study, the anti-inflammatory activity and non-toxicity of Sechium edule extract (SEE) were tested by measuring the expression level of NO, PGE₂, and pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) in lipopolysaccharide (LPS) and Sechium edule extract-treated in RAW 264.7 macrophages. Sechium edule extract inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner but without compromising cell viability. In addition, we confirmed that the inhibition activity of Sechium edule extract on the production of NO and PEG2 was via the downregulation of iNOS and COX-2, respectively. Moreover, expression levels of the phosphorylation of Mitogen-activated protein kinase (MAP kinase) family such as c-Jun Ntermical kinases (JNK) and p38 were reduced by Sechium edule extract. Our results clearly indicate that Sechium edule extract can be a potential new source for anti-inflammatory drugs and healthcare product ingredients.