Diabetes affects many aspects of gastrointestinal motility, in part due to changes in interstitial cells of Cajal (ICC). The effect of diabetes on the colon, however, is not well characterized, and the aim of the present study was to investigate possible relationships between altered colonic motility as a consequence of streptozotocin-induced diabetes and injury to ICC. Physiological, immunohistochemical, and ultrastructural techniques were employed. The motor pattern of the rat colon was dominated by rhythmic high-amplitude, low-frequency contractions that were primarily myogenic in origin. These rhythmic contractions were induced by stretch associated with increased tension; the amplitude of the superimposed rhythmic contractions increased with increasing applied tension. In diabetic rats, the stretch-induced rhythmic contractile activity remained robust and of similar frequency but was significantly higher in amplitude compared with that in control rats. At 700 mg of applied tension, the force of contraction in circular colonic muscle strips of the diabetic rats was 370% of control values. This robust presence of low-frequency contractions is consistent with the unaffected pacemaker, the ICC associated with Auerbach's plexus, and the increased amplitude correlates with loss of and injury to ICC of the submuscular plexus and intramuscular ICC. Loss of inhibitory nitrergic nerves does not appear to be a factor based on unaltered nNOS immunoreactivity.