Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), and is associated with multifocal demyelination and axonal injury in the central nervous system (CNS). Damage of neuronal network is responsible for neuronal deficits, thus, remyelination and axonal remodeling are required for recovery of neuronal function. Recent studies have indicated that neuronal deficits are often followed by spontaneously recovered due to the reconstruction of neuronal network. Therefore, determining how reconstruction of neuronal network occurs under pathologic conditions has a potential to identify new therapeutic avenues for treating CNS disease. We focused on the role of angiogenesis, which is a promising feature in the pathological CNS environment. We revealed that prostacyclin (prostaglandin I2), which is a vasodilator derived from vascular endothelial cells, acted on oligodendrocyte precursor cells and corticospinal axon via IP receptor. IP receptor activation promoted remyelination and axon regeneration by a mechanism dependent on 3'-5'-cyclic adenosine monophosphate (cAMP) synthesis. Moreover, prostacyclin signaling was involved in recovery of neuronal function following CNS inflammation. These findings suggest that targeting the molecule that is associated pathological CNS environment provide a therapeutic benefit for treating MS.