〔Abstract〕 Objective To screen the target of helicid in the intervention of depression based on network pharmacology and molecular docking, and to study the effect of helicid on the expression level of related targets in hippocampus, prefrontal cortex, striatum and habenular nucleus of chronic unpredictable mild stress(CUMS) rats. Methods The target of helicid was predicted by SwissTargetPrediction database, and the depression related targets were screened by GeneCards、DisGeNet、TTD and DRUGBANK databases; the metascape platform was used for gene enrichment analysis, and the "helicid-depression-pathway" network was constructed; Autodock Vina was used for molecular docking research; qRT-PCR was used to detect the effect of helicid on the mRNA expression of HTR1 A, ADORA1 and ADORA2 A in rat tissues. Results The 81 helicid targets and 1 640 depression targets were obtained, including 40 intersecting targets; the key targets were mainly enriched in cAMP signal pathway, PI3 K-Akt signal pathway, MAPK signal pathway and so on; the results of molecular docking showed that the binding activity of helicid with most targets was good; helicid up-regulated the expression levels of HTR1 A, ADORA1 and ADORA2 A mRNA in hippocampus, prefrontal cortex, striatum and habenular nucleus of CUMS rats. Conclusion Helicid may act on cAMP, PI3 K-Akt, MAPK and other signal pathways to intervene depression through HTR1 A, ADORA1 and ADORA2 A.