Diabetic neuropathy, a major complication of diabetes mellitus, is associated with development of gastrointestinal motility dysfunction and autonomic neuropathy. N-hexacosanol has neurotrophic effects and exhibits a wide variety of biological actions. In this study, we investigated the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on streptozotocin-diabetic hypercontractility in the rat ileum longitudinal muscles. Treatment with N-hexacosanol did not alter the diabetic status of the animals, i.e., body weight, serum glucose, and serum insulin levels, but significantly restored the thickness of intestine wall and ameliorated diabetes-induced hypercontractility of the rat ileum in a dose-dependent manner. Furthermore, N-hexacosanol reversed the diabetes-induced upregulation of intestinal muscarinic M(2) and M(3) receptors mRNAs in the streptozotocin-diabetic rats. These results indicate that N-hexacosanol has therapeutic effects on hypercontractility in the diabetic ileum by ameliorating overexpression of muscarinic M(2) and M(3) receptors mRNAs.