Fibrostenosis complicates Crohn’s disease in the 30-50% of patients with a Montreal B2 phenotype. Current medical therapies can delay but no prevent critical fibrostenosis and the need for surgery. Transforming growth factor-β1 (TGF-β1)-induced excess extracellular matrix (ECM) protein production in ileal subepithelial myofibroblasts (SEMF) are a major structural component of fibrosis. The role of endoplasmic reticulum (ER) stress in the pathogenesis of Crohn’s disease has been delineated in epithelial and lamina propria mononuclear cells and more recently we have delineated the role of ER stress in SEMF of fibrostenotic ileum.