The mechanisms underlying the changes in blood-brain barrier (BBB) integrity in septic encephalopathy are poorly understood. The present study was designed to examine whether hyperbaric oxygen therapy (HBOT) influences the response of BBB to sepsis induced by cecal ligation and puncture (CLP) in rats. Cerebral cortical and hippocampal tissue levels of tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA) and glutathione (GSH) levels were measured. BBB permeability was functionally and structurally evaluated by determining extravasation of Evans blue (EB) and horseradish peroxidase (HRP) tracers, respectively. Immunohistochemistry and western blotting for occludin were performed. HBOT did not alter TNF-alpha levels in CLP operated rats while a significant decrease was noted when the therapy was subjected to intact rats. MDA levels in animals subjected to CLP plus HBOT were significantly decreased. In septic rats, the decreased GSH levels were significantly increased by HBOT. While HBOT attenuated the increased BBB permeability to EB in rats subjected to CLP (P<0.01), no macroscopic alteration was observed in the enhanced HRP extravasation. An increase in HRP extravasation was also observed by HBOT in intact animals. Occludin immunoreactivity and expression remained essentially unchanged in the brain capillaries of animals in all groups. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in brain capillary endothelial cells of animals treated with CLP and/or HBOT. In conclusion, our results revealed that HBOT did not provide overall protective effects on the BBB integrity in septic conditions and even led to BBB disruption in intact animals. (C) 2011 Elsevier B.V. All rights reserved.