Objective To investigate the protective effect of estrogen on rats with experimental allergic encephalomyelitis （EAE） and its association with the adhesion molecule CD44.Methods A total of 40 rats were randomly divided into normal control group， EAE group， and high- and low-dose estrogen treatment groups， with 10 rats in each group. The rats were observed in terms of disease onset and pathological changes of brain tissue， and immunohistochemistry was used to measure the content of CD44 in brain tissue.Results The rats in the EAE group and the high- and low-dose estrogen treatment groups had disease onset with different severities， but the high- and low-dose estrogen treatment groups had milder clinical symptoms than the EAE group. Immunohistochemistry showed varying degrees of the expression of CD44-positive cells in the white matter and gray-white matter junction of the central nervous system （CNS） in the EAE group and the high- and low-dose estrogen treatment groups. Image analysis showed that compared with the EAE group， the high- and low-dose estrogen treatment groups had a significant reduction in the expression of CD44 in the CNS white matter （P<0.01）， and compared with the low-dose estrogen treatment group， the high-dose estrogen treatment group had a significant reduction in the expression of CD44 in the CNS white matter （P<0.01）.Conclusions There is high expression of the adhesion molecule CD44 in the multiple sclerosis animal model of EAE， and estrogen may exert a protective effect on EAE rats by inhibiting the expression of the adhesion molecule CD44.