Schmeda-Hirschmann, G.; Astudillo L. Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla Talca, 747, Chile. Rodriguez, J. Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile.Purpose: Previous work demonstrates that oleanolic acid (OA), a triterpene widely distributed in plants, shows gastroprotective effect in the ethanol, aspirin and pilorous ligature-induced gastric ulcer in rats as well as in the ethanol/hydrochloric acid-induced ulcer in mice. The aim of this work was to assess the healing effect of OA in the acetic acid-induced chronic gastric ulcer model in rats. Methods: Chronic gastric lesions were induced in male Sprague–Dawley rats with acetic acid. OA was administered orally during 14 days at 25, 50 and 100 mg/kg per day. Ranitidine (50 mg/kg) and the vehicle were used as controls. The ulcer area (mm2) and the curative ratio (%) were determined. Histological preparations were carried out for comparative purposes. Results: The effect of OA was significantly different as compared to the control reducing the lesion area (in mm2) from 39±7 in controls to 17.8±1.9 and 9.4±1.1 at the doses of 50 and 100 mg/kg, respectively. The curative ratio was 54.5 and 76% for the compound at 50 and 100 mg/kg, while ranitidine at 50 mg/kg reduced the lesion area to 6.9±0.8 with a curative ratio of 84%. Mucosal thickness increased from 342 μm in controls to 540 μm in oleanolic acid- (100 mg/kg) and 945 μm in ranitidine-treated animals. Histological examination of the stomach showed regeneration of the lesions. Conclusions: OA improves healing of chronic gastric lesions in rats. The low toxicity and widespread occurrence of OA in plants suggest a potential for the development of the triterpene or their derivatives as a new antiulcer drug.