Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) mice are used to model the disease progression of MS and mirror MS-like pathology. Previous researches have confirmed that inhibition of NLRP3 inflammasome significantly alleviated the severity of EAE mice and the demyelination of spinal cord, but its effect on neuronal damage and oligodendrocyte loss in the brain remains unclear. In this study, female C57BL/6 mice were immunized with MOG35-55 and PTX to establish experimental autoimmune encephalomyelitis (EAE) model. MCC950, a selective NLRP3 inflammasome inhibitor, was used to investigate the effect of NLRP3 inflammasome on the pathological changes and glial cell activation in the brain of EAE mice by immunohistochemistry. Our results demonstrated that MCC950 ameliorated the neuronal damage, demyelination, and oligodendrocyte loss in the brain of EAE mice. This protective effect of MCC950 may be attributed to its ability to suppress the activation of glial cells and prevents microglia polarization to M1 phenotype. Our work indicates that inhibition of NLRP3 inflammasome has the therapeutic effects of neuroprotection through immunomodulation and is a promising therapeutic strategy for MS.