Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.