Based on the phenomenon that colonic exposure to therapeutic radiation can result in relevant intestinal brosis, radiation-induced models of intestinal brosis were invented. Radiation-induced thickening of the bowel wall is characterized by an enlarged submucosa, increased proliferation rates of broblasts and smooth mus­cle cells as well as enhanced accumulation of collagen and other ECM elements [46]. Core features of radiation-induced intestinal brosis are vascular sclerosis with endothelial dysfunction and chronic ulcers. Of note, the degree of brosis can increase up to 26weeks following radiation and is mainly inuenced by the applied radiation dose, fraction size as well as the time between several radiation procedures [47, 48]. Two different experimental settings for this approach have been proposed. In the rst model, a small bowel segment is resected, exernally irradiated and the re-implanted into the animal [49, 50]. In an alternative approach, a 4-cm segment of the distal ileum is transferred into the scrotum after a orchiectomy has been per­formed; since this location is easy accessable for radiation [51]. The radiation results in an acute inammatory response with colitis und ulcer development and induction of brotic alterations in the stromal compartment. This multicellular­mediated response is partially dependent on inammation with microvascular insults being an early stimulus that is accompanied by subsequent hypoxia [52]. Subsequently, common brotic alterations including probrotic cytokine produc­tion such as TGF-β1 and CTGF, broblast proliferation and increased collagen pro­duction are observed [53]. In addition, activation of mast cells, Rho-associated kinase (ROCK) signaling pathways, endothelial dysfunction and activation of capsaicin- sensitive nerves represent additional, more specic response of the irradi­ated bowel [54].