Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract has received little attention to date compared with external smooth muscle layers. Motor activity of the muscularis mucosae shows a great regional and species difference. Autonomic innervation profile is also different from esophagus to colon or between animal species. Intracellular transduction mechanisms for motor activity of the muscularis mucosae are also different from those of external longitudinal and circular muscles or from vascular and airway smooth muscles. Since the submucosal area is a major source for eicosanoid production, abnormality of muscularis mucosae motor activity may link with abnormality of mucosal absorption and secretion functions. Inflammatory bowel diseases such as diarrhea, irritable bowel syndrome and Crohn's disease accompanied with altered motor activity of the muscularis mucosae. Much attention should be attracted to the human muscularis mucosae as a new therapeutic target for inflammatory bowel diseases.