The pathophysiology of wound healing in the bowel wall suggests that collagen and matrix metalloproteinases (MMPs) have an important role in the changes of the bowel wall seen in several colonic diseases. Several recent studies suggest that disturbances of the collagen texture and the extracellular matrix (ECM) metabolism are major factors leading to the onset of diverticular disease. Changes of the ECM also play a role in the development of inflammatory bowel diseases. Regarding the permanent remodeling of the bowel wall, any imbalance of the ECM could support the onset of chronic inflammation and the development of fistula formation, such as that seen in patients with Crohn's disease. Disturbances of the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery and suggest the presence of a genetically defined risk population with disturbed wound healing mechanisms. This concept could explain the well known situation where an anastomotic breakdown is observed, despite the absence of other known risk factors and after a technically correct anastomosis.