Abstract: Multiple sclerosis (MS) is an autoimmune and chronic inflammatory disease characterized by plaques, areas of destroyed myelin sheaths in the CNS, which results in multiple disabilities for patients. In addition to demyelinated plaques, pathophysiological studies have shown “shadow plaques” that represent areas of partial remyelination. New myelin can be made by oligodendrocytes (OLs) generated from oligodendrocyte progenitor cells (OPCs) that pre-exist in the demyelinated area or recruited from surrounding areas. To successfully repopulate the demyelinated area, OPCs have to proliferate, migrate, and differentiate into mature OLs capable of forming myelin. Identifying factors that influence remyelination is a current topic in developmental neurobiology. Previously, we showed that Golli proteins, which have a broad distribution in the nervous and immune systems, are present both in OPCs and activated microglia around MS lesions. We hypothesized that in response to inflammation, Golli proteins may promote proliferation of OPCs through microglial cells. To test this, we established neonatal mouse brain slice and cell cultures and used lipopolysaccharide (LPS) to induce inflammation. In LPS-treated brain slices, Golli proteins displayed increased expression in the cortical subventricular zone. Furthermore, Golli proteins were demonstrated only in the conditioned medium from LPS-treated microglial cell cultures (LPS-MCM), and were absent in either conditioned medium from LPS-treated astrocytes or control media. Finally, proliferation of purified OPCs was promoted with LPS-MCM or Golli proteins, but not with LPS alone. In summary, these results demonstrate that activated microglia are beneficial for proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process.