In summary, this study found that electroacupuncture regulates the IL‐4‐JAK1‐STAT6 signaling pathway, inhibits abnormal microglia activation, promotes their polarization towards the M2 phenotype, alleviates neuroinflammation, and improves depressive‐like behaviors in mice with IBD and comorbid depression. Here, STAT6 is linked to depressive symptom measurement.