In this study, we explored whether taVNS could improve depression‐like behaviors and suppress neuroinflammation in chronic unpredicted mild stress (CUMS)‐exposed rats, and further explored the molecular mechanisms underlying the action of taVNS, whether its antidepressant effect based on anti‐inflammation is mediated by the regulation of α7nAchR via JAK2/STAT3/NF‐κB signaling pathway. This evidence concerns the gene STAT3 and major depressive disorder.