Abstract： Objective To investigate the effect of simulated weightlessness on ultrastructural changes and oxidative stress in gastric mucosa of tail-suspended rats.Methods Eighty-eight healthy male Wistar rats were divided into 11 groups (n=8 each) by random number table,and tail-suspension was used to simulate the weightlessness in animal models.The duration of tail-suspension in each group of rats was 0 h (normal control group),6 h,12 h,1 d,2 d,3 d,5 d,7 d,14 d,21 d and 28 d respectively.After theexperiment,the pathologic changes of gastric mucosa in rats of each group were studied,and the content ofsuperoxide dismutase (SOD),malondialdehyde (MDA) and nitric oxide (NO) in the gastric mucosa were detected.Immunohistochemical assay was used to examine the expression of inducible nitric oxide synthase (NOS2) and cyclooxygenase 2 (COX2).Results Transmission electron microscopy revealed nuclear shrinkage of gland cells,condensation of chromatin around the perinuclear membrane,mitochondrial swelling,rupture and lysis of cristae,vacuolar degeneration and dilatation of the rough endoplasmic reticulum in gastric mucosa of tail-suspended rats under simulated weightlessness.These changes were significant in groups of 14 d,21 d and 28 d suspension.Compared with the normal control group,the content of SOD increased obviously in the gastric mucosa of rats with tail-suspension for 1 d,5 d,14 d,21 d and 28 d (all P＜0.05),as did the content of MDA in those for 12 h,14 d,21 d,28 d (all P＜0.05),and the content of NO in those for 12 h,2 d,3 d,5 d,14 d and 28 d,respectively (all P＜0.05).Immunohistochemistry showed enhanced expression of both NOS2 and COX2 in the gastric mucosa of rats with tail suspension for 6 h,12 h,1 d,and 2 d,which then declined until resurging on 14 d,21 d and 28 d.Conclusion Simulated weightlessness can induce ultrastructural alteration,changes of NOS2 and COX2 expressions in gastric mucosa of tail-suspended rats.