The polysaccharide (PS) fractions from several medicinal herbs have been reported to have antiulcer effects against experimental ulcer in the rat. The watersoluble PS fractions from G. lucidum (Reishi mushroom) have been shown to inhibit indomethacin-induced gastric mucosal lesions in rats. This study aimed to investigate the effect of the PS fraction from G. lucidum on the healing of gastric ulcer induced by acetic acid in the rat and to elucidate the underlying mechanisms involved. The abdomen of rats was incised and the stomach treated with 10 M acetic acid (100 l) for 1 min, and then treated with G. lucidum PS (0.1, 0.5 or 1.0 g/kg) intragastrically, once a day for 14 consecutive days. The results indicated that the oral administration of G. lucidum PS at 0.5 and 1.0 g/kg for 2 weeks caused a significant acceleration of the ulcer healing by 40.1% and 55.9%, respectively. In the mechanistic studies, additional rats were treated with 10 M acetic acid to induce acute ulcers, and then treated with G. lucidum PS (1.0 g/kg) for 3, 7, 10 or 14 days. Exposure of the rat stomach to acetic acid led to decreased mucus and increased prostaglandin levels. Treatment of G. lucidum PS at 1.0 g/kg significantly (P < 0.05) suppressed or restored the decreased gastric mucus levels and increased gastric prostaglandin concentrations compared to the control group. These results indicates that G. lucidum PS is an active component with healing efficacy on acetic acid-induced ulcer in the rat, which may represent a useful herbal preparation for the prevention and treatment of peptic ulcers.