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Background: The purpose of this study was to verify physiological, end-organ and systemic inflammatory changes in zone II after resuscitative endovascular balloon occlusion of the aorta (REBOA) in a normovolemic rabbit model.Methods: Anaesthetized rabbits were subjected to aortic balloon occlusion for different times (15 min, 30 min, 60 min and 90 min) followed by 2 h of reperfusion. Rabbits with no balloon occlusion were set as the control group. ELISAs were used to examine the serum levels of ALT, AST, Cr, BUN, MDA, SOD, IL-8, IL-6, and TNF-α; HE staining was used to identify the morphological changes in the kidney; RT-PCR was used to detect the mRNA levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus; and Western blotting was used to measure the protein expression levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus.Results: Plasma concentrations of liver markers, kidney markers, inflammatory factors and oxidative stress indicators were significantly increased at the end of reperfusion in the 30 min, 60 min and 90 min groups. Damage to the kidney occurred in the 30 min, 60 min and 90 min groups. The mRNA and protein expression levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus were significantly increased at the end of reperfusion in the 30 min group, and as the time of occlusion extended, these levels continued to increase.Conclusion: Activation of systemic inflammation and ischaemia-reperfusion injury of end-organs occurred when the occlusion time reached 30 min. Therefore, 15 min should be regarded as a safe period of REBOA in zone II.