In the present study, we investigated the effect of ginseng extract (KRG) and total saponins (GTS) on microglial activation. KRG and GTS inhibited LPS-induced expression of iNOS, MMP-9 and proinflammatory cytokines in microglial cells. Suppression of microglial activation by ginseng was also observed in the mouse brain inflamed by LPS. Furthermore, KRG and GTS significantly suppressed NF-kappaB and MAP kinase activities, which are upstream signaling molecules in inflammation. Among the individual ginsenosides tested, Rh2, Rh3 and compound K significantly inhibited LPS-induced iNOS and cytokine expressions. Therefore, the inhibition of microglial activation by ginseng saponins may a good potential therapeutic modality for neurodegenerative diseases.