Objective To investigate the effects of alcoholic extract of Hemerocallis citrina Baroni on the depressive-like behaviors in zebrafish larvae (Danio rerio) induced by reserpine. Methods Zebrafish larvae were divided into various groups: control (Con) group, reserpine group, fluoxetine group, H. citrina alcohol extract (HCE) low dose group ( 1. 5 mg / L), HCE medium dose group ( 3 mg / L), and HCE high dose group ( 4. 5 mg / L). Depressive-like behaviors were analyzed using sound and light stimulation. Real-time PCR was used to investigate the effects of HCE on depression related astrocyte markers (GFAP, C3, C4B, EMP-1, S100α-10) and the neurotrophic factor BDNF and its receptor genes (P75, TrkB). Results In comparison to the control group, the model group demonstrated significantly shorter movement distance and reduced movement time under sound and light stimulation ( P<0. 05, P<0. 001, P<0.0001). Following the administration of HCE, zebrafish larvae exhibited significantly heightened sensitivity to light and sound stimulation compared to the model group (P<0. 05, P<0. 0001). Astrocyte marker genes were up-regulated in the model group zebrafish brains compared to the control group ( P<0. 0001 ). However, when the model group was administered HCE, the expression of astrocyte markers was significantly down-regulated compared to the model group (P<0. 0001). Neurotrophic factor and its receptor genes (BDNF, P75, TrkB) were down-regulated in zebrafish brains in the model group compared to those in the control group ( P<0. 0001). However, in the group administered HCE, the expression of BDNF, P75, and TrkB was significantly up-regulated compared to that in the model group (P<0. 01, P<0. 0001). These findings suggest that HCE suppressed the inflammatory responses caused by astrocyte activation and promoted the production of neurotrophic factors and their receptor genes, thereby exerting an ameliorative effect on depression. Conclusions Alcoholic extracts of H. citrina can ameliorate the depression-like behavioral changes induced by reserpine in zebrafish larvae. They reduce the expression of astrocyte markers in the zebrafish brain and promote the production of neurotrophic factors and their receptor genes, playing an antidepressant role.