Intestinal fibrosis is a pathological consequence of excessive myofibroblast proliferation and collagen deposition, frequently seen in Crohn’s disease. It is considered as an excessive repair response to injury and inflammation, but not always to be fully correlated with the severity of inflammation. Therefore it needs a better understanding of underlying mechanisms of hyper-proliferation of myofibroblasts in inflammatory bowel disease. In this study, we found that systemic administration of an mTOR inhibitor rapamycin or specific mTOR deletion in mononuclear phagocytes (CX3CR1+) inhibited expression of IL23 and IL-1, along with reduced intestinal production of IL22 and fibrosis in chronic TNBS fibrosis mouse model.