The heartwood of Acer tegmentosum(Acereaceae) has been used as a Korean traditional medicinal drug against alcohol poisoning and hepatitis. To find the biologically active substance in A. tegmentosum heartwood, we investigated the protective effects of the heartwood extract and its constituents on pain and gastropathy in mouse. In these experiments, salidroside, a major compound, significantly reduced gastric lesion and pain in mice. Oral administration of salidroside at the 10 and 20 mg/kg doses greatly reduced the gastric lesion induced by HCl/ethanol (inhibitory effect, 51.5 and 68.8%, respectively) and by indomethacin/bethanechol (inhibitory effect, 31.3 and 38.8%, respectively). Salidroside also stabilized pH of gastric juice and the increase of gastric juice secretion and total acid output. Taken together, these results demonstrated that salidroside is the main ingredient of A. tegmentosum heartwood to prevent gastric lesion and pain that can be caused by drinking alcohol.