Cirsii Japonici Herba(CJ) is a wild perennial herb found in many areas of Korea as well as China and Japan, which has been used to treat bleeding and inflammation. Silibinin is the main flavonoid extracted from milk thistle (Cirsii Japonici Herba). It exhibits potent antioxidant activity and anti-inflammatory effect. In this study, the effect of CJ and silibinin extract on lipopolysaccharide-induced inflammation was investigated using MTS assay, RT-PCR, western blot, and nitric oxide detection on mouse BV2 microglial cell lines. In the present results, CJ and silibinin extract suppressed nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of COX-2 and iNOS gene expression in BV2 cells. Moreover, CJ and silibinin also repressed some lipopolysaccharide-induced signaling molecules. Importantly, catalase-induced COX-2 and iNOS expression needed activations of $NF-{kappa}B$, PI3K/Akt, and MAPK, which were important for the transcriptional up-regulation of COX-2 and iNOS. CJ and silibinin interaction on BV2 cells down-regulated $NF-{kappa}B$-dependent proinflammatory cytokine (IL-2,IL-6) expression. They are involved in the regulation of inflammatory responses. These data shows that CJ and silibinin exerts anti-inflammatory and analgesic effects, probably by suppression of COX-2 and iNOS synthase expression in BV2 microglial cells.