OBJECTIVE： To study the protective effect of sivelestat sodium on experimental autoimmune encephalomyelitis （EAE） model rats. METHODS： 60 Wistar rats were randomly divided into normal control group （normal saline）， model group （normal saline）， positive drug group [prednisone acetate tablets 5 mg/（kg·d）] and sivelestat sodium low-dose， middle-dose and high-dose groups [5， 8， 10 mg/（kg·d）] with 10 rats in each group. Except for normal control group， other groups were given guinea pig spinal cord homogenate as antigen to produce EAE model， and then given relevant medicine ip since the same day of modeling， for consecutive 16 d. The neurologic function of mice was scored， and pathological changes of brain and spinal cord were observed； the content of IFN-γ， IL-4， CCL3， chemotactic factor CCL5 regulating and activating normal T cell expression and secretion were determined. RESULTS： Compared with normal control group， neurological function score and the content of IFN-γ， CCL5 and CCL3 increased， while IL-4 content decreased （P＜0.01）； myelinoclasis and inflammatory cell infiltration occurred. Compared with model group， neurological function score and the content of CCL3 and CCL5 decreased in positive drug group and sivelestat sodium low-concentration， medium-concentration and high-concentration groups （P＜0.01）； both myelinoclasis and inflammatory cell infiltration relieved； the content of IFN-γ decreased， while IL-4 content increased in positive drug group and sivelestat sodium high-concentration group； IL-4 content increased in sivelestat sodium medium-concentration group （P＜0.01）； there was no statistical significance in other groups （P＞0.05）. Above effect depended on drug dose. CONCLUSIONS： Sivelestat sodium can relieve myelinoclasis and inflammatory cell infiltration， and the mechanism may be related to the decrease of IFN-γ content， the increase of IL-4 content， and inhibition of CCL3 and CCL5 expression in peripheral blood.