Objective To observe the expression patterns of Src-suppressed C kinase substrate (SSeCKS) in rat models of experimental autoimmune encephalomyelitis (EAE), and investigate the possible functions of SSeCKS in the pathogenesis to find new therapeutic strategies against EAE and multiple sclerosis (MS). Methods The model was prepared in Lewis rat induced by myelin basic protein (MBP). The rats were sacrificed at different phase after immunization. Inflammatory cell infiltration was observed by HE staining. Western blot was used to detect the changes of SSeCKS expression during EAE and the distribution of SSeCKS in spinal cord of EAE rats was investigated by immunohistochemisty staining. Results Monophasic EAE process was induced by MBP in Lewis rats. EAE onset in rats occurred during the days 7 to 10 after immunization, peaked at the days 13 to 16, and exhibited spontaneous remission until the day 30. The rats at peak of EAE presented significant inflammatory cell infiltration, but restored their pathological phenotype in the recovery phase. The expression of SSeCKS exhibited low level in the spinal cord of normal rats and CFA controls, but markedly increased from E1 stage to remission phase with a peak at the E3 stage after EAE induction. SSeCKS was found to locate in neurons and glias. Conclusion The rat model of EAE was successfully established. SSeCKS expression changed during EAE course, which suggested SSeCKS may involve in the development of EAE.