Abstract: Objective To investigate the effect of Leptin on differentiation of nueral stem cell and explore the underline molecular mechanism. Methods Co-culture neural stem cell with different concentration of Leptin (0, 0.05, 0.2, 0.5, 1, 2 mg/L), the effect of Leptin on differentiation of nueral stem cell was analyzed. After treated the nueral stem cell with inhibitors of Jak-STAT3 〔Janus family tyrosine kinases (Jak kinases) and signal transducers and activators of transcription (STAT proteins) 〕and PI3k-Akt 〔phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)〕, the STAT3, phosphorylated-STAT3, Akt, phosphorylated-Akt levels and GFAP were detected with western blot and fluoroimmunoassay respectively. Results Morphology observation found nueral stem cell to change to astrocyte. An increased astrocyte marker (GFAP) in Leptin group but not Tuj-1 or MBP with fluoroimmunoassay and western blot detection was observed. The expression of GFAP began at 24 h after co-culture, and increased consistent with the concentration of Leptin. Jak-STAT3 inhibitors but not PI3k-Akt inhibitors decreased the expression of phosphorylated-STAT3, and accompanily decreased the expression of GFAP. Conclusion Leptin may have an effect on the astroglial differentiation on neural stem cells through the JAK-STAT3 pathway but not PI3k-Akt pathway.