Objective:To investigate the changes of interstitial cells of Cajal(ICC) and hemeoxygenase-2(HO-2) in the colon of diabetic rats and the immunocolocalization of the ICC and HO-2 in the colon of rats,and discuss the possible mechanism of colon dysfunction associated with diabetes mellitus. Methods:The distribution and expressions of ICC and HO-2 in the proximal and distal colon tissues of rats were detected by immunohistochemistry. Immunolocalization of ICC and HO-2 was detected by confocal laser scanning microscopy. Results:ICC and HO-2 were mainly distributed in the myenteric plexus of the colon tissue,and the expressions of ICC and HO-2 in the proximal and distal colon tissues of diabetic rats were decreased compared with those in the control group(P < 0.05). Double immunofluorescence displayed that c-kit positive cells and HO-2 positive cells were expressed in the identical sites in the colon tissues of rats. Double expressions of ICC and HO-2 in the colon tissues of diabetic rats were decreased compared with those in the control group. Conclusion:Decreased expressions of ICC and HO-2 in the colon tissues might play an important role in the pathogenesis of colon dysfunction associated with diabetes mellitus; ICC may produce CO and intervene its role in the gastrointestinal motility.