This study examined whether Salvianolic acid B (Sal B), a major active component of Chinese herb Radix Salviae Miltiorrhizae, may exert an anti-inflammatory effect in microglia and may be neuroprotective by regulating microglial activation. Our results showed that Sal B significantly reduced the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and reactive oxygen species (ROS) induced by lipopolysaccharide (LPS) treatment in rat primary microglia in a dose-dependent manner. Sal B had no effects on ATP-dependent IL-1beta release and interferon (IFN)-gamma-induced NO production. Sal B also suppressed LPS-induced inducible nitric oxide synthase (iNOS), TNF-alpha, and IL-1beta mRNA expression, which was accompanied by inhibiting transcription factor NF-kappaB activation. Sal B could protect neurons through inhibition of microglial activation in a microglia-neuron coculture system. In conclusion, these data demonstrate that anti-inflammatory activity of Sal B in microglia contributes to its neuroprotective effect and suggest that it may be useful for preventing microglia-mediated neuroinflammation.