As shown in the present study, rats exposed to stress showed activation of the LepR-STAT3 signaling pathway in the ARC, as evidenced by upregulation of JAK2 and STAT3, suggesting that the LepR-STAT3 signaling pathway in the ARC is involved in the pathology of depression induced by CUMS and susceptibility to glucose intolerance. Here, JAK2 is linked to major depressive disorder.