Multiple sclerosis (MS) is a chronic inflammatory disease occurring in the central nervous system (CNS). Literature suggests that acupuncture may play a role in the treatment of MS, although its mechanism remains unclear. In this study, we observed that acupuncture significantly alleviates central lesions and delays the progression of experimental autoimmune encephalomyelitis (EAE, an animal model of MS). Conducting a proteomics analysis of murine brain, we found that acupuncture notably suppresses the expression of certain proteins associated with astrocyte functions, including their activation, antigen processing and presentation, as well as myelination. Additionally, we observed a significant increase in POMC expression in the acupuncture group. POMC is the precursor of ?-endorphin, which can influences the activation and antigen presentation function of astrocytes. Therefore, our study indicates that acupuncture, by modulating the expression of POMC, influences the activation and antigen presentation function of astrocytes, thereby alleviating inflammation in the CNS. These findings contribute to a deeper understanding of the immunomodulatory mechanisms through which acupuncture acts on MS.