Multiple sclerosis is a chronic autoimmune disease of the CNS characterized by multifocal inflammation in the brain, extensive demyelination, axonal loss, and gliosis. Although, the exact pathogenesis of MS remains to be completely elucidated, CD4+T cell-mediated autoimmunity has been accepted as one of the most important aspects of MS pathogenesis (Lazibat et al., 2018). Microglia are resident immune cells in the CNS. In MS microglial are not only involved in CNS damage caused by immune response, but also play an important role in disease recovery and nerve regeneration (Zrzavy et al., 2017). NPY, through its Y1 receptor, can inhibit microglial activation, IL-Iβ production, as well as subsequent NF-κB-iNOS signal transduction, decrease the production of NO (Sørensen et al., 2012). NPY can also reduce the migration and phagocytosis of microglia by limiting the activity of microglia and avoiding excessive release of NO, glutamate, cytokines, and other cytotoxic substances from microglia. This effect is achieved by affecting the p38 signal system. It is also associated with heat shock protein 27 (Ferreira et al., 2012). Remarkably, NPY can inhibit the secretion of IFN-γ and enhance IL-4 secretion of murine lymphocytes, indicating that NPY shifts the help T cell 1 (Th)1/Th2 balance toward the Th2 phenotype (Levite, 2008). It was found that the levels of NPY were decreased in the cerebrospinal fluid of MS patients (Maeda et al., 1994).