Objective:To observe the effect of acupuncture on experimental autoimmune encephalomyelitis ( EAE) mice and the effect on the expressions of brainstem phosphorylated P38 mitogen-activated protease, and to explore the effect and mechanism of acupuncture on multiple sclerosis(MS), and to provide the theoretical support for treatment of MS. Methods:40 mice of C57BL/6 were randomly divided into the blank control group, the EAE model group, the acupuncture treatment group, and the hormone treatment group. EAE model was established in C57BL/6 mice by complete antigen prepared from myelin oligodendrocyte glycoprotein35-55(MOG35-55) except for the blank group. Since the 14th day after modeling, the blank group and the model group were grasped and fixed, and given by gavage with physiological saline every day. The hormone group were given by gavage with prednisone. Acupuncture group received acupuncture at “Dazhui” point, bilateral “Shenshu” point, bilateral “Zusanli” point. Recording the weight and neurological function score of each group. On the 28th day, the pathological changes in brain tissue were observed by Luxol Fast Blue( LFB) myelin staining method, the expressions of p-p38MAPK in brain tissue were measured by immunohistochemistry method and western blot. Reaults: Compared to the blank group, the weights of the other groups were lower(P＜0.05); the neurological function scores were higher(P＜0.05); the degrees of demyelination were higher; the expressions of p-p38MAPK by immunohistochemical analysis and western blot test were higher(P＜0.05).Compared to the model group, the weights of the acupuncture group and hormone group were higher(P＜0.05); the neurological function scores were lower(P＜0.05); the degrees of demyelination were lower; the expressions of p-p38MAPK by immunohistochemical analysis and western blot test were lower(P＜0.05). Compared to the hormone group, the weight of the acupuncture group was lower(P＜0.05); the neurological function score was higher(P＜0.05); the expressions of p-p38MAPK by immunohistochemical analysis and western blot test were higher, but with no statistical difference(P＞0.05). Conclusion: Acupuncture can reduce the inflammation of EAE mice and alleviate the extent of nerve damage. It may be related to lowering the expression of p-p38MAPK.