Abstract: OBJECTIVE To study the effect of butylphthalide(NBP) on the differentiation of neural stem cells into neural cells through PI3K-AKT signaling pathway. METHODS The neural stem cells were isolated and cultured from the cerebral cortex of SD rats. Cultivation in complete medium for differentiation. The neural stem cells were identified by light microscopy and Nestin immunofluorescence. Set the control group and the experimental group, the experimental group was supplemented with NBP to assist differentiation and divided into low dose group(NBP 1 μmol·L^-1), medium dose group(NBP 5 μmol·L^-1) and high dose group(NBP 10 μmol·L^-1). After 24 h, the viability of neural stem cells was detected by CCK-8, and the differentiation ability of neural stem cells was detected by alkaline phosphatase staining. The results differentiation of neural stem cells detected by MAP2 immunofluorescence, RT-qPCR detected the mRNA expression levels of transcription factors-SOX2, PAX6 and NeuN. The expression of PI3K-AKT signaling pathway was detected by Western-blot and RT-qPCR. RESULTS The activity of neural stem cells was increased and the differentiation ability of the neural stem cells was strengthened. The alkaline phosphatase test was strongly positive. The expression levels of transcription factors SOX2, PAX6 and NeuN mRNA were increased, and the expression levels of PI3K-AKT signaling pathway protein and mRNA were increased, they all showed a dose-dependent. CONCLUSION NBP can promote the differentiation of neural stem cells into neural cells, and its action may be related to the activity of PI3K-AKT.