Silibinin is the major pharmacologically active compound of silymarin, the Silybum marianum fruit extract. Hepatoprotective activities of silibinin/silymarin are well-known, and recent studies demonstrated their anti-inflammatory and anti-carcinogenic effects which are due to inhibition of the transcription factor NF-${kappa}B$. Based on this knowledge, we hypothesized that silibinin could be effective in the treatment of multiple sclerosis (MS) and so we tested its immunosuppressive effect in experimental autoimmune encephalomyelitis (EAE), the MS animal model. The process of spinal cord demyelination and inflammation were observed and T cell migration was determined by FACS analysis. The results showed that silibinin significantly reduced the histological signs of demyelination and inflammation in EAE. Since cytokines play an important role in inflammatory disease, the proliferative response and cytokine production were examined in lymphocytes from spleens and lymph nodes. We demonstrated that silibinin Agnonspecifically down-regulated the secretion of pro-inflammatory Th1 cytokines and up-regulated the anti-inflammatory Th2 cytokines in vitro. Silibinin also dose-dependently inhibited the production of Th1 cytokines ex vivo. These results indicate that silibinin is both immunosuppressive and immunomodulatory.