Multiple sclerosis (MS) is a neurodegenerative and demyelinating autoimmune disease mediated by autoreactive T cells that affects the central nervous system (CNS). Electroacupuncture (EA) has emerged as an alternative or supplemental treatment for MS, but the mechanism by which EA may alleviate MS symptoms is unresolved. Here, we examined the effects of EA at the Zusanli (ST36) acupoint on mice with experimental autoimmune encephalomyelitis (EAE), the predominant animal model of MS. The effects of EA on EAE emergence, inflammatory cell levels, proinflammatory cytokines, and spinal cord pathology were examined. EA treatment attenuated the EAE clinical score and associated spinal cord demyelination, while reducing the presence of proinflammatory cytokines in mononuclear cells (MNCs), downregulating microRNA (miR)-155, and upregulating the opioid peptide precursor proopiomelanocortin (POMC) in the CNS. Experiments in which cultured neurons were transfected with a miR-155 mimic or a miR-155 inhibitor further showed that the direct modulation of miR-155 levels could regulate POMC levels in neurons. In conclusion, the alleviation of EAE by EA is characterized by reduced proportions of Th1/Th17 cells and increased proportions of Th2 cells, POMC upregulation, and miR-155 downregulation, while miR-155 itself can suppress POMC expression. These results, support the hypothesis that the effects of EA on EAE may involve the downregulation of miR-155.