Increasing evidence indicates that adipose tissue is an active endocrine organ involved in metabolic syndrome and regulation of inflammation. Visceral fat accumulation is a hallmark of both obesity and Crohn's disease. Here, we present recent data describing the immune properties of intra-abdominal adipose tissue that could link the innate immune response to obesity-related disorders and gut inflammation. Innate immune properties of adipocytes have become well characterized since recent studies described the Toll-like receptor (TLR) expression repertoire and specific TLR ligand responses of adipocytes. Adipokine secretion profiles have also been elucidated both in obese patients, when they may be involved in obesity-associated metabolic disease, and in Crohn's disease. Whereas mesenteric fat hypertrophy and fat wrapping of the bowel are characteristic of Crohn's disease, there exists a paucity of information concerning this important pathophysiological aspect. Our current classical animal models are of limited interest when investigating the role of mesenteric fat in gut inflammation. Recent new alternative disease paradigms could help to design more specific models for elucidating chronic transmural inflammation of the gut. Obesity and Crohn's disease share common features with the development of mesenteric fat that may be involved in gut inflammation. Further studies are required to clearly assess the origin and influence of intestinal fat deposits upon gut inflammation, notably during Crohn's disease development.