The etiology of inflammatory bowel disease and, in particular, Crohn's disease involves a deregulated mucosal immune system under the influence of intestinal flora and environmental factors in genetically susceptible individuals. A new hypothesis has focused on mesenteric fat hypertrophy and the presence of ectopic fat surrounding inflamed bowel, the so-called creeping fat, which are hallmarks of Crohn's disease. Mesenteric adipose tissue is currently recognized as an active actor in immunity with a capacity for mediator secretion. These mediators include classic pro- and anti-inflammatory cytokines or chemokines and hormone-like adipokines with multiple effects. Mesenteric fat participates in the course of Crohn's disease and may play an active role in the regulation of intestinal inflammation. However, little is known about the origin and role of mesenteric fat in Crohn's disease, essentially because of a lack of experimental models that develop creeping fat. The purpose of this review is to present the recent data describing the immune properties of mesenteric fat and the recent advances in animal models, which have suggested a new hypothesis about the role of creeping fat in Crohn's disease.