Objective To explore the anti-inflammatory mechanisms of selective estrogen receptor modulator (SERM) on experimental autoimmune encephalomyelitis(EAE). Methods EAE models were induced with MOG35-55 peptide in 60 mice and all animals were ovarectomized. The model animals were then divided into treatment group and control group (n=30). Treatment group was treated with SERM. The clinical symptom scores were compared between the two groups. The pathologic changes of the brain and spinal cord were studied by H-E staining and luxol fast blue(LFB)-HE staining. The expressions of MMP-9, TNF-α, IFN-γ, and IL-4 mRNA and protein were examined by quantitative real-time PCR and ELISA. Western blotting analysis was used to analyze the expression of myelin basic protein (MBP) so as to analyze the demyelination status.Results Clinical symptom scores and incidence of EAE in the treatment group were improved compared with those in the control group (P<0.01, P<0.05). H-E staining showed that infiltration of inflammatory cells was decreased in the treatment group (P<0.05). LFB-H-E staining and Western blotting analysis showed that the demyelination was improved in the treatment group (P<0.05). The results of quantitative real-time PCR and ELISA showed that the expression of MMP-9,TNF-α, and IFN-γ were decreased and the expression of IL-4 was increased (P<0.05, P<0.01). Conclusion SERM can alleviate the inflammation symptom in EAE mice through decreasing MMP-9, TNF-α, and IFN-γ and increasing IL-4 expression.