Objective To observe the trend of differentiation of neural stem cells (NSCS) at different time points after oxygen glucose deprivation / reoxygenation (OGD/ R) and its correlation with Erythropoietin Receptor (EPOR), β- Common Receptor (βCR) and PDZ-binding-kinase (PBK). Methods The primary neural stem cells of mice were isolated and the OGD model was made. The OGD was hypoxia for 3 hours, reoxygenation for 1 hour, 2 hours, 4 hours, 6 hours and 8 hours. The differentiation trend of neural stem cells was observed. CNP and MBP, GFAP and S100B, RBFOX3, MAP2 and TUBB3,EPOR, CSF2RB and PBK were detected by RT-PCR and Pearson correlation analysis was carried out. Results 1, OGD treatment promoted the differentiation of neural stem cells to oligodendrocytes, and the expressions of CnP</i> and MbP</i> were increased obviously at 4 h after OGD. 2, OGD treatment promoted the differentiation of neural stem cells to astrocytes, and the expression of GfaP</i> was decreased at 2~ 6 h after OGD, while the expression of GfaP</i> was increased at 1 h and 8 h after OGD. The expression of S100b was significantly increased at 2~ 8 h after OGD. 3, OGD treatment reduced neuronal differentiation of neural stem cells, and the expression of RBFOX3 and TUBB3 were decreased after OGD significantly at 2 h and 6 h after OGD. 4, Pbk was reduced at 1 h and 8 h after OGD. EPOR and Pbk were positively correlated with the expression of CnP</i>, and Pbk was positively correlated with the expression of MbP</i>. Conclusions Hypoxia injury significantly promoted the formation of oligodendrocytes and astrocytes and inhibited the neuronal differentiation of neural stem cells. Epor and Pbk may be involved in the differentiation of neural stem cells to oligodendrocytes. These result may provide a basis for the further research on the related mechanism of nerve regeneration after ischemia.