Since gastric mucosal membrane, that is the most important part of mucosal barrier, is a lipid-protein layer, ionized and water-soluble NSAIDs are restricted in their transport. In the highly acidic condition of gastric juice, however most of NSAIDs are non-ionized and fat-soluble, dissolve rapidly in lipid-protein layer, and is rapidly absorbed from the acid gastric contents. Within the gastric mucosal cells in neutral condition, NSAIDs are ionized and H+ ions are released. Intracellular NSAIDs cause impairment of gastric mucosal barrier by reduction and alteration of mucous secretion and/or reduction of mucosal ATP. Intracellular H+ ions provoke the mast cells to release histamine which causes mucosal micro-vascular damage. Finally, auto-digestion by gastric juice in this impaired mucosa makes the variegated mucosal lesions.