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This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness.Twenty-four Wistar rats were randomly divided into three groups:CON group (n=8),control; SUS-14 d group (n=8),tail-suspension for 14 days;SUS-21 d group (n=8),tail-suspension for 21 days.Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR.Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry.Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups.The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group,and significantly lower than those in CON group (Occldin:0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1:0.82±0.01 vs 1.00±0.02 vs 1.55±0.01,P＜0.01).Moreover,the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group,and significantly higher than those in CON group (DAO:27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate:37.86±0.74 vs 28.26±1.01 vs 17.76±0.91,P＜0.01).There were significant negative co rrelations between occludin or ZO-1 expression levels and DAO (r2=0.9014,r2=0.9355,P＜0.01) or d-lactate levels (r2=0.8989,r2=0.9331,P＜0.01).Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model.The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.