Objective：This study aims to investigate the effects of serine/threonine protein kinase 25(STK25)on the activation of astrocytes as well as the process of experimental autoimmune encephalomyelitis(EAE)in mice. Methods：The EAE mouse model was induced by myelin oligodendrocyte glycoprotein 35-55(MOG_{35 - 55})polypeptide. The transcription levels and the expression of STK25， tumor necrosis factor- α(TNF-α)and interferon inducible protein 10(IP-10)in spinal cord tissue and serum were detected by ELISA， Real -time PCR and Western blot，respectively. The expression of STK25 in astrocytes in spinal cord tissue of mice was detected by immunofluorescence double staining. Primary mouse astrocytes were stimulated in vitro with interferon-γ(IFN-γ)，and the expression of STK25 and the transcription levels of cytokines were detected by the above methods at different times. Primary mouse astrocytes were transfected by recombinant lentiviral vector，and stimulated with IFN - γ，the transcription levels of TNF - α and IP - 10 were measured. Meantime，the EAE model was induced after injecting vectors 7 days，and the expression of STK25 in spinal cord tissue was detected by Western blot，the transcription levels of TNF - α and IP - 10 were detected by Real - time PCR，and the infiltration of inflammatory cells and the demyelination of spinal cord were observed by HE and Luxol fast blue(LFB)staining methods，respectively. Results：Compared with control group，the transcription level and the expression of STK25 in EAE group were significantly reduced while the levels of inflammatory cytokines and chemokines were significantly increased. Moreover，the expression of STK25 in astrocytes in spinal cord was significantly reduced. The expression of STK25 in astrocytes was decreased after stimulated by IFN-γ in vitro，and the production of inflammatory cytokines were increased. After specific knocking down endogenous STK25 in astrocyte，the production of inflammatory cytokines and chemokines in vitro astrocytes and in vivo EAE mice were increased significantly，which exacerbated the inflammatory cell infiltration and myelination of spinal cord tissue in EAE mice. Conclusion：STK25 may participate in the pathological process of EAE mice by affecting the activation of astrocytes and regulating the production of inflammatory cytokines and chemokines.