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. This evidence concerns the gene STAT3 and depressive disorder.