Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease. During demyelination, oligodendrocyte precursor cells (OPCs) can proliferate, migrate to the site of injury, differentiate into mature oligodendrocytes, and generate new myelin. Since increased numbers of OPCs are observed in MS lesions, insufficient differentiation of OPCs is considered to be one of the causes of demyelination and axonal degeneration. However, it has been reported that OPCs could promote the disruption of the BBB or release inflammatory cytokines under inflammatory conditions, and the involvement of OPCs in MS is not fully understood. In this study, we investigated the role of OPCs in the acute phase of MS by removing OPCs. We employed a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein (35-55). We depleted OPCs by intraperitoneally injecting tamoxifen and diphtheria toxin (DT) in Pdgfra^CreER/+:Rosa26^DTR/+ mice. When DT was injected from the next day of disease onset, EAE severity was significantly reduced in OPC-depleted mice. Quantitative RT-PCR analysis revealed that the expression levels of pro-inflammatory cytokines and the marker of helper T cell subset Th17 were suppressed in the spinal cord of OPC-depleted group. These data suggest that OPCs are involved in CNS inflammation, T cell response and the development of EAE.