Infections and inflammations in the gut are often connected to extra-intestinal manifestations in distant organs such as liver, joint, pancreas, eye, and skin. Although several factors including genetic inheritance, gut microbiota, and epithelial permeability have a role in the etiopathogenesis of these extra-intestinal diseases, aberrant and harmful accumulation of leukocytes in the distant organs directly causes the inflammatory symptoms. In this chapter, we concentrate on the mechanisms regulating the traffic of gut-derived lymphocytes to liver, joint, and pancreas and present the most recent achievements in drug development aiming at controlling harmful leukocyte trafficking in clinical trials.