Hormonal imbalance causes depressive behaviours in chronic mental disorders. The use of natural products to relieve depressive symptoms is getting attention due to its minimal side effects and multiple health benefits. The present study aims to test the hypothesis that Camellia nitidissima Chi leave extract (CNC) could have antide-pressant effects and whose underlying mechanisms could be related to promote hippocampal neurogenesis. Firstly, we conducted quality control study and identified 17 active compounds in the CNC extract. Then, we performed a series of behaviour tests to evaluate the antidepressant effects in a chronic corticosterone (CORT)-induced depressive mouse model. CNC extract significantly ameliorated CORT-induced depressive behaviours, whose effects were similar to sertraline. Interestingly, CNC extract decreased the levels of CORT and ACTH in the plasma and increased 5-HT in plasma and hippocampus. CNC extract promoted adult hippocampal neurogenesis in the CORT-treated mice in vivo. The neurogenic effects of CNC were also confirmed in primary cultured hip-pocampal neurons and hESCs with CORT challenge in vitro. Furthermore, CNC enhanced the phosphorylation of Akt, GSK3 beta and CREB in the hippocampus of CORT-treated mice in vivo as well as CORT-treated PC12 cells in vitro. Co-treatment of wortmannin abolished the effects of CNC. Taken together, CNC could be an effective functional food to stimulate hippocampal neurogenesis for anti-depressant treatment. The neurogenic mecha-nisms could be related to regulating hypothalamic-pituitaryadrenal axis and activating Akt/GSK3 beta/CREB signaling pathway.