The present study shows that miR‐204‐5p deficiency contributes to the enhancement of neuroinflammation and apoptosis which are involved in the pathogenesis of depression‐like behaviors via activating JAK2/STAT3 signaling pathway, while overexpression of miR‐204‐5p significantly ameliorates the neuronal deterioration and behavioral disorders in rats. The gene discussed is JAK2; the disease is major depressive disorder.