Macrophages are essential immune cells for the maintenance of tissue homeostasis in the intestinal mucosa barrier. They are also involved in dysregulated process of wound healing, particularly in the context of intestinal damage and tissue repair in inflammatory bowel diseases. Phenotypic plasticity of macrophages from classical M1 to alternative M2 is regulated by a variety of inflammatory cytokines including IFN-γ and IL-4. The IL-4-derived M2 can further differentiate into myofibroblasts. Activated alpha-smooth muscle actin (α-SMA) positive-myofibroblasts are central to the wound healing process and in patients with fibrostenotic Crohn’s disease.