We evaluated the changes in interstitial cells of Cajal (ICCs) and myenteric nerve system in relation to the activity and number of muscularis resident macrophage at a level of myenteric nerve plexus in the Crohn's disease model treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the TNBS-treated rat colon, ICCs network and also myenteric nerve system were damaged or disappeared in the inflamed region. The number of ED2-immunoreactive resident macrophage significantly increased where the ICCs or myenteric nerve systems changed. Although resident macrophage appeared morphologically ramified in control intestine, TNBS-treatment changed it to round shape, possibly an indication of functionally activated state. In fact, the round shape of macrophage expressed marked MHC class II comparing ramified macrophage in control intestine. Physiological study indicated that the motility index, the amplitude and frequency of spontaneous contractions were significantly decreased in the TNBS-induced colitis intestine. Moreover, the index of peristalsis observed in whole proximal colon tissue was inhibited by the treatment with TNBS. Electron microscopic analysis indicated that the contour of the myenteric ganglia became irregular in TNBS-treated rat colon, and numerous macrophages were observed around the ganglia. Similar results were obtained in the Hirschsprung's disease colitis model rats. In conclusion, the inhibition of spontaneous contractions and peristalsis in circular smooth muscle from TNBS-induced colitis rat colon may be attributable to the impairment of ICCs and myenteric nerve systems. Because of an indication of the macrophage activation and the close correlation between the degeneration and macrophage accumulation, it is suggested that the macrophages are involved in the degenerative pathology of intestinal motility.