The purpose of this study was to investigate the effects and mechanisms of 17beta-estradiol pharmacological postconditioning on gastric epithelial cells hypoxia/reoxygenation injury by using an in vitro model of human gastric epithelial cells. The model of hypoxia/reoxygenation was established with human gastric epithelial cell line. The gastric epithelial cell viability was detected by 3-(4, 5-dimethylthazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Gastric epithelial cellular apoptosis was determined by Hoechst 33258 fluorochrome staining and flow cytometric analysis. Contents of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by Colorimetry analysis. The protein expression of Bcl-2 and Bax in different groups was determined by Western blot analyses and immunocytochemistry assay. 17beta-estradiol (10(-8), 10(-7) and 10(-6)mol/l) inhibited hypoxia/reoxygenation injury and 17beta-estradiol (10(-6)mol/l) obviously attenuated hypoxia/reoxygenation injury 3h hypoxia followed by 4h reoxygenation. 17beta-estradiol promoted gastric epithelial cell viability and inhibited the gastric epithelial cell apoptosis, and meanwhile, decreased the MDA content and increased SOD activity. The level of Bcl-2 protein was restored to the normal level by 17beta-estradiol pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by 17beta-estradiol pharmacological postconditioning. These effects of 17beta-estradiol were inhibited by pretreatment with fulvestrant. These data suggested that 17beta-estradiol seems involved in regulation of gastric hypoxia/reoxygenation injury and gastroprotection, and its protective effects were strongly related to estrogen receptor.