The present study evaluates the effect of grifolin (GFL) in oxygen/glucose deprivation (OGD) induced white matter lesion. Injury induced with OGD was found to be significant at the 9th h of OGD induction and the effect of GFL on the proliferation of oligodendrocyte precursor cells (OPCs) was assessed by CCK-8 and Hoechst 33258 assay at GFL 1, 5, 25, 50 and 100 mu m concentrations. Whereas immunocytochemistry was performed for the assessment of survival and apoptosis of OPCs, western blot assay and RT-PCR were performed after 8th day of OGD injury for the estimation of expressions of myelin basic protein (MBP) and inhibitor of DNA binding 2 (Id2) in OPCs respectively. Results of the study suggests that treatment with GFL significantly enhances the survival rate and decreases the apoptosis of OPCs in OGD induced injury model. Immunocytochemical staining of Oligodendrocyte transcription factor (Olig2) and Bromodeoxyuridine (Brdu) shows that GFL treatment improves the proliferation of OPCs than OGD group. Moreover data of western blot assay suggested that treatment with GFL significantly enhances the expressions of MBP and Olig2 than OGD. It was observed that expressions of Id2 decreases and Olig2 enhances in GFL treated group than OGD group. Data of our study concludes that GFL enhances the differentiation and proliferation of OPCs in OGD-induced injury by altering the expressions of Id2 and Olig2.