The 'IN' of chronic inflammation-that is, the mechanisms of cell entry into the intestinal mucosa, bacterial and foreign antigen invasion, angiogenesis, and the control of gut inflammation through intestinal microvasculature-has received a great deal of attention in studies of the pathogenesis of inflammatory bowel disease (IBD). This has resulted in the validation of several targets for the treatment of experimental inflammation-both on immune and non-immune cells-some of which have translated into effective treatments for patients with IBD. An important aspect of this has been our growing understanding of the role the intestinal vascular microcirculation plays in the initiation and perpetuation of the inflammatory process, by regulating the migration of leucocytes into the interstitial space. However, it is becoming increasingly clear that it is also important to focus on the 'OUT' of chronic inflammation-that is, the lymphatics and their role in controlling tissue oedema, leucocyte exit, bacterial antigen and inflammatory chemokine clearance. As our understanding of the lymphatics and the role they play grows, another rich source of non-immune cell targets for therapeutic intervention is gradually being revealed. This article describes current knowledge of the roles played by the vascular and lymphatic endothelium throughout the gut in the pathogenesis of IBD, and how this differs from their role under physiological conditions, as well as discussing current and future therapeutic targets that have been identified.