Objective To investigate the effect of estrogen on experimental allergic encephalomyelitis (EAE) in rats.Methods Thirty male rats were randomly divided into three groups: EAE model group, high-dose estrogen treatment group, and low-dose estrogen treatment group, with 10 rats in each group. The high- and low-dose estrogen treatment groups were subcutaneously injected with estradiol benzoate 1 mg/kg/d and 250 μg/kg/d, respectively, for ten days. Clinical symptoms of the rats were observed, and the pathological changes in cerebral and spinal cord tissues were observed by HE staining.Results The high-and low-dose estrogen treatment groups showed milder clinical symptoms as compared with the EAE model group, including lower incidence, longer delitescence, shorter progression period, milder neurological dysfunction at the peak stage of disease, and reduced infiltration of inflammatory cells into cerebral and spinal cord tissues. The protective effect was more obvious in the high-dose estrogen treatment group.Conclusions Estrogen has a protective effect on the multiple sclerosis model of EAE, and the effectiveness is positively correlated with dosage.