To elucidate the anti-ulcer mechanism of mezolidon (KM-1146, 2-(3,4-dimethoxyphenyl)-5-methylthiazolidine-4-one), we investigated gastric mucosal blood flow (laser-Doppler method), transmucosal potential difference, gastroduodenal mucosal surface pH and blood viscosity in rats under a water-immersion stress condition. In the control group, gastric mucosal ulcers occurred three hours after the onset of water-immersion. At that time, gastric mucosal blood flow decreased to 40% and the potential difference decreased to 48%. In the mezolidon-pretreated group, gastric mucosal ulcers were significantly reduced, and the potential difference was significantly higher than in the control group. Gastric mucosal blood flow increased significantly to 120% twenty minutes after the onset of water-immersion and then decreased, but was significantly higher than in the control group. Gastroduodenal mucosal surface pH was not affected by the pretreatment with mezolidon under this condition. Pretreatment with mezolidon did not affect blood viscosity. In conclusion, the anti-ulcer effect of mezolidon may involve the increase and/or maintenance of gastric mucosal blood flow, but more investigations are necessary to understand the mechanism involved.