Objective To investigate the role of extracellular signalregulated kinase (Erk) and transcriptional factors such as c-fos, c-jun in B104 CMinduced oligodendrocyte progenitor cells (OPCs) differentiation from neural stem cells (NSCs). Methods The effect of U0126, the specific inhibitor of Erk1/2, on B104 CM induced OPC differentiation from NSCs was observed by morphology. The phosphorylation of Erk1/2 and mRNA expression of transcriptional factors c-fos, c-jun and c-myc in NSCs in the control group, B104 CM treated group and U0126 preincubated group were detected by Western blotting and RT-PCR methods respectively. Results B104 CMinduced OPC differentiation from NSCs could be blocked by preincubation of U0126 Treatment of NSCs with B104 CM produced a rapid increase in phosphorylation of Erk1/2 and an upregulation of c-fos andc-jun mRNA expression, which could be blocked by the preincubation of U0126 Conclusion B104 CM instructs oligodendrocyte differentiation from NSCs through the activ