In the present study, we discovered that the expression levels of leptin and LepRb were significantly increased in the colon after EPSD, TNBS, and CUMS stimulation, which was consistent with the high leptin content in the serum, suggesting that leptin influences the development of colonic inflammation, fibrosis, and depression-like behavior in PI-IBS rats. The gene discussed is LEP; the disease is irritable bowel syndrome.