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Objective To investigate the effects of all-trans-retinoic acid (ATRA) on signaling pathway and regulations of neural stem cells (NSCs) in adult mice and the effects on the family of cytochrome P450 (CYP450). Methods NSCs were isolated from the sub-ventricular zone ( SVZ) of brain in adult mice and then were cultured. The cells were divided into the ATRA group and blank control group. The ATRA group was added with 10-6 mol/L ATRA. Flow cytometry (FCM) was used to detect the cell surface markers in the two groups, and we calculated the percentage of neurons, astrocytes ,oligodendrocytes and the percentage of NSCs accounting for total cells. The real-time PCR was used to detect the related gene expression of CYP450 family, and we screened statistically significant gene. ELISA was applied to detect the activity of cytochrome P450 reductase (CPR). The expression levels of P38 and p-P38 were detected by using Western blotting. Results In the ATRA group, NSCs mainly differentiated into neurons, and some differentiated into astrocytes, with less differentiation of oligodendrocytes. Compared with the blank control group, the expression of CYP26A1 , CYP26B1 and CYP26C1 in the P450 family genes of the ATRA group was up-regulated (all P<0.05). The activity of CPR and the expression of p-P38 protein in the ATRA group were higher than those in the blank control group (both P<0. 05). Conclusion ATRA promotes the differentiation of mouse NSCs into neurons, and it may play a regulatory role by up-regulating the CYP26 family genes in CYP450 and increasing CPR activity and the P38 MAPK pathway. [ABSTRACT FROM AUTHOR]