Background:: Adipose tissue is recognized as a compartment secreting highly active molecules. Creeping fat represents a characteristic feature of Crohn's disease (CD). Proinflammatory or anti‐inflammatory adipose‐derived secretory products, now generally called adipocytokines, may play a role in the pathogenesis of CD. Materials and Methods: Adipose tissue specimens were obtained from creeping fat contiguous to the involved intestine of 10 patients with CD. Mesenteric adipose tissue specimens resected from 13 patients with colon cancer (CC) and from 7 patients with diverticulitis served as controls. Three fat tissue specimen per well and 6 to 8 wells per patient were incubated ex vivo for 24 h. The release of adiponectin, resistin, leptin, interleukin‐6, macrophage colony‐stimulating factor, monocyte chemotactic protein‐1, and migration inhibitory factor was measured by ELISA. The expression of AdipoR1 and AdipoR2 receptors was investigated by real‐time quantitative polymerase chain reaction in a subset of adipose tissues. Results: The secretion of adiponectin and macrophage colony‐stimulating factor, as well as leptin and migration inhibitory factor, was significantly upregulated in CD compared with CC and diverticulitis or CC only, respectively. Resistin, interleukin‐6, and monocyte chemotactic protein‐1 were not specifically induced in CD but were associated with unspecific inflammation. Adiponectin receptor expression was not different in CC, CD, or diverticulitis. Steroid treatment in CD patients had differential effects on the ex vivo secretion of adipocytokines. Conclusions: A specific secretion pattern of proinflammatory and anti‐inflammatory adipocytokines indicates the significance of adipose tissue in intestinal inflammation in CD. Future investigations of this intestinal compartment may provide novelinsights into the pathophysiological role of creeping fat and CD.