Objective:To establish a stress ulcer model by seawater immersion and restriction in rats, and to investigate the mechanism of preconditioning on stress ulcer and the effect of different stressing periods on the ulcer. Methods: A total of 60 male Wistar rats were equally divided into 6 groups , namely, the normal control group (Group A) , direct stress group(Group B), precondition groupⅠ (Group C), precondition groupⅡ(Group S), precondition group Ⅲ (Group E), and ranitidine group (Group F).Precondition peroids of C,D,E groups were 0.5 h/d,1 h/d,and 1 h/d,respectively, for 5 days. Stress time in E group was 10 h,and in B,C,D,and F groups were 8 h. Radioimmunoassay was used to determine the sera levels of endothelin (ET) and 6-dk-dPGF1α in rats. Ulcer index was calculated by Guth method; the ulcer lesion tissues were collected for further pathological examination. Results: The sera ET levels in group C, D and F were lower than those in group B（P<0.01，P<0.05，and P<0.01, respectively）. The sera 6-dk-dPGF1α levels in group C, D and F were significantly higher than those in group B（P<0.01，P<0.05，and P<0.01, respectively）. The ulcer indices in group C, D and F were significantly lower than those in group B（P<0.01，P<0.05，and P<0.01, respectively）. The pathological results were improved in group C, D, and F compared with those in group B. Conclusion: Preconditioning can effectively reduce the rat stress ulcer,but long-time stressing may offset the protective effect of precondition.