Adiponectin (ApN) is an adipocytokine predominantly secreted by adipocytes. Normal serum adiponectin levels have been shown to be important for anti-inflammation, but the role of local adiponectin expression in colon and in conditions of colonic inflammation such as Hirschsprung’s associated enterocolitis is not well described. Previous data from our lab using pooled microarray analysis of human colonic samples of normal and Hirschsprung’s disease patients revealed a 12 fold lower expression in adiponectin expression between aganglionated and ganglionated colon. Currently, we have found a differential spatial expression across normal colon, inflamed colon and colon of Hirschsprung’s disease (HD) models in mice. METHODS. Immunohistochemistry for ApN, E-cadherin, and fibroblast marker was performed across the length of the colon of wildtype mice, mice with HD (Lethal spotting mice) and mice treated with dextran sodium sulfate (DSS) to cause colitis. Real-time PCR for adiponectin, adiponectin receptors R1 and R2, and GFAP (a glial cell marker to assess for ganglionated bowel) was also performed in these groups in sequential colonic sections. RESULTS. Adiponectin expression was localized to the muscularis and submucosal layers of colon with minimal to no colonic epithelial expression. This expression colocalized to the myofibroblasts and smooth muscle cells of the colonic wall. Adiponectin expression varied along the length of the colon with the proximal colon having consistently the greatest expression and the more distal colon having significantly less expression. Mutant mice and mice treated with DSS have similarly lower levels of adiponectin compared to controls. Adiponectin receptor expression did not vary along the length of colon nor were there significant differences between colonic epithelium and muscularis layers. CONCLUSIONS. Adiponectin but not adiponectin receptor expression varies along the length of the colon and is greatest within the colonic muscularis. The significance of this differential compartmental expression is unknown, however, the expression pattern of adiponectin in normal mice is similar to the compartment specific presence of colonic bacteria. This differential colonic adiponectin expression may be helpful to protect regions of the colon from bacterial invasion and inflammation. Adiponectin expression is also lower in murine models of inflammation and abnormal enteric nervous system development and did not reach normal levels in the ganglionated sections of colon of the mice with HD. Whether low adiponectin expression correlates with Hirschsprung’s associated enterocolitis has yet to be determined.