1. We investigated the effect of hyperbaric oxygenation (HBO2) pretreatment on the production of exhaled nitric oxide (ENO) and the expression of lung inducible nitric oxide synthase (iNOS) by Escherichia coli lipopolysaccharide (LPS)-induced shock in an experimental rat model. 2. Rats were randomized into four groups, anaesthetized, mechanically ventilated with room air and infused with normal saline (2 mL/h) through the jugular vein for 5 h. Group 1 (NS) received only normal saline. Group 2 (HBO2-NS) was pretreated with HBO2 at 2.8 absolute atmospheres for 2 h and then received normal saline. Group 3 (LPS) received LPS, 20 mg/kg, i.v., bolus. Group 4 (HBO2-LPS) was pretreated with HBO2 for 2 h, followed by LPS. 3. Arterial blood gases, blood pressure, blood pH and ENO production were measured every 30 min. Plasma nitrite/nitrate (NOx) concentrations were assessed at the beginning (baseline) and at the end of the study. Lung myeloperoxidase (MPO) activity, iNOS expression and histological scores were measured for the evaluation of lung injury. 4. Administration of LPS was associated with decreased blood pressure and pH, increased ENO production, plasma NOx concentrations, lung iNOS expression and MPO activity. 5. Pretreatment with HBO2 significantly alleviated the LPS-induced hypotension, acidosis and decreased ENO production, plasma NOx concentrations, lung MPO activity and expression of iNOS. Hyperbaric O2 had no effect on control rats. 6. Our data show that HBO2 pretreatment has beneficial haemodynamic effects in rats with endotoxin shock. The beneficial effects of HBO2 may be partially mediated by decreased ENO production via reduced LPS-induced lung iNOS expression.