Inflammatory response in the central nervous system mediated by the activation of microglia is a key event in the early stages of the development of neurodegenerative diseases.Lipopolysaccharide (LPS) has been reported to cause marked microglia activation.It is very important to develop drugs that can inhibit microglia activation and ncuroinflammation.Here, we investigated the inhibitory effect of schisandrin, one of the major dibenzocyclooctadine lignans extracted from Schisandra Chinensis BAILL., against LPS-induced inflammatory responses in microglia.Schisandrin inhibited LPS-induced production of nitrite oxide (NO) and prostaglandin E2 (PGE2) in a concentrationdependent manner.The protein and mRNA expression ofiNOS and COX-2 in response to LPS application were also decreased by schisandrin.In addition, schisandrin effectively reduced LPS-induced expression of the mRNA for the proinflammatory cytokines, TNF-α, IL-1 β and IL-6.Schisandrin significantly reduced nuclear factor-κB (NF-κB) translocation in LPS-stimulated N9 microglia.Further more, schisandrin inhibited LPS-induced the degradation of the inhibitor κB (IκB) as well as the mitogen-activated protein kinase (MAPKs) phosphorylation.To summarize, these results suggest that schisandrin suppresses the induction of cytokines by LPS, as well as iNOS and COX-2 expression, by blocking NF-κB and MAPKs activation.Thus, schisandrin has an anti-inflammatory activity in microglia, and may have a therapeutic potential for the treatment ofneuroinflammatory diseases.