Objective：This study aims to investigate the possible mechanism by which vitamin D（VD） regulates the secretion of neurotransmitters in hippocampal neurons. Methods：The serum levels of 25 hydroxyvitamin D［25（OH）D］，5-hydroxytryptamine（5-HT）and norepinephrine（NE）were detected by chemiluminescence and enzyme immunoassay （ELISA） in 62 postpartum depression（PPD）patients and 31 healthy pregnant women. The proliferation of hippocampal neurons was determined by methylthiazolyltetrazolium（MTT）colorimetric method. Western blotting was used to detect the expression of total Akt（T-Akt）and phosphorylated Akt（p-Akt）. Results：The serum levels of 25（OH）D，5-HT and NE in the mild depressed group were lower than those in the healthy control group，and the differences were statistically significant（all P < 0.05）. The serum levels of 25（OH）D，5-HT and NE in the severe depression group were significantly lower than those in the mild depression group（all P < 0.05）. VD had a significant dose-dependent effect on the proliferation of hippocampal neurons and the levels of secreted 5-HT and NE in vitro. In addition，the proliferation and secreted 5-HT and NE levels of neurons were significantly different between VD+negative small interfering RNA（siRNA）group and control group（all P < 0.05）. In the VD+VD receptor（VDR）siRNA group，there was no statistically significant difference in proliferation of neurons and the levels of 5-HT and NE when compared with contrd group（all P > 0.05）. Western blot results showed that the expression of phosphorylated Akt in the VD+negative siRNA group was significantly increased when compared with control group，with statistical differences（P < 0.01）. There was no significant difference in the expression of phosphorylated Akt between the VD+VDR siRNA group and control group（all P > 0.05）. In the VD+DMSO group，the proliferation of neurons and the levels of 5-HT and NE were significantly different when compared with control group（all P < 0.05）. However，there was no significant difference in proliferation of neurons and the levels of 5-HT and NE between VD+LY294002（inhibitor of PI3k/Akt signaling pathway） group and control group（all P > 0.05）. Conclusion：VD promotes the activity of hippocampal neurons and secretion of 5-HT and NE，which may be related to the activation of PI3k/Akt signaling pathway. That plays an important role in the clinical prevention and treatment of PPD and postpartum care.