Objective: Using arecoline as the research object, the mouse depression model induced by chronic unpredictable mild stress was used to explore the anti-depressive activity of arecoline in vivo and the possible mechanism of its action, so as to provide data support for the nutritional and health care value of arecoline and provide theoretical basis for the development and utilization of arecoline resources. Methods: 60 quarantine qualified SPF C57/BL6 mice were randomly divided into blank group, model group, fluoxetine hydrochloride group (20mg/kg), arecoline low, medium and high dose groups (10, 20 and 40mg/kg) according to body weight, with 10 mice in each group. The effects of arecoline on the behavior of depressed mice were evaluated by open field, tail suspension and forced swimming.Corticosterone (Cort) content in serum, Superoxide dismutase (SOD) in serum and brain tissue of mice was detected by enzyme-linked immunoassay.Malondialdehyde (MDA), Catalase (CAT) levels and 5-hydroxytryptamine (5-HT), norepinephrine (norepinephrine) levels in brain tissue(NE), dopamine (DA), gamma-aminobutyric acid (GABA), tumor necrosis factor (TNF-α), interleukin-10 (Interleukin-10)Biochemical indices such as IL-10 and interleukin-1β (interleukin-1β);The expressions of BDNF, TrkB and CREB were detected by Western blot. The results showed that arecoline could significantly reduce the total distance and average speed of the model mice in the open field, and increase the number of mouse activities. The immobility time of model mice in tail suspension and forced swimming experiments was significantly reduced.Arecoline significantly decreased the level of serum corticosterone, increased the level of SOD and CAT, and decreased the level of MDA. The levels of 5-HT, DA, NE and GABA were significantly increased. The levels of cytokines TNF-α, IL-6 and IL-1β were significantly decreased.The expression levels of brain-derived neurotrophic factor（BDNF）, tropomyosin receptor kinase B（TrkB） and cAMP-response element binding protein（CREB） in the brain tissue of mice were significantly increased.Conclusion: Arecaline has significant anti-depressant activity, and its mechanism is related to anti-oxidative stress injury, inhibition of neuroinflammatory response, regulation of neurotransmitter levels and BDNF/TrkB/CREB signaling pathway.This study explored the antidepressant effect of arecoline for the first time and initially revealed its possible regulatory mechanism, which can provide data support for the neural activity of arecoline and lay a theoretical foundation for the medicinal development of arecoline.