Objective: To investigate the anti-depression mechanisms of fish oil by using network pharmacology. Methods: The targets for the treatment of depression with fish oil were obtained from databases such as the PharmMapper， SwissTargetPrediction， DrugBank， GeneCards， and Disgenet. The potential targets protein interaction network was analyzed using String website and Cytoscape software. Enrichment analysis of potential target proteins was performed using the DAVID 6.8 database. Additionally， a visual network diagram of the component-target pathway was created using Cytoscape software. Results: Fish oil exhibited anti-depression effects mainly through EPA and DHA. A total of 115 relevant targets for the treatment of depression were identified， including MAPK3， MAPK1， CASP3， PPARG， PPARA， PTGS2， DRD2， among others. These main targets play an anti-depressant role via regulating signal pathways， such as serotonergic synapse， PPAR signaling pathway， arachidonic acid metabolism， neuroactive ligand-receptor interaction and influencing biological processes， such as response to drug， steroid hormone mediated signaling pathway， oxidation-reduction process. Conclusion: Fish oil treatment for depression is characterized by its action on multiple targets and pathways， potentially involving the serotonergic synapse， PPAR signaling pathway， neuroactive ligand-receptor interaction， and arachidonic acid metabolism pathways to exert its anti-depressant effects.