Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination and inflammation lesions. MS predominantly affects young adults with a high incidence of disability. However, the exact pathogenesis of MS is still not clear. Studies found that microglia polarization tending to pro-inflammatory M1-like state during the onset of MS, causing the M1/M2 ratio imbalance, forming pro-inflammatory microenvironment state, and which further leading to nervous tissue damage ultimately. Microglia polarization may be considered as the initiator of pathologic alterations by releasing pro-inflammatory cytokines and secondarily trigger the initial microglia response. Given the pivotal role of imbalanced microglia polarization in MS initiation, a critical review of microglia polarization is presented here, in order to elucidate the pathogenesis of MS and highlight the noteworthy candidate therapeutic targets for clinic treatment.