Aim To investigate the nenuroprotective effects of hydrogen-rich saline on brain injury of acute carbon monoxide （CO） poisoned rats. Methods Adult male Sprague-Dawley rats were randomly assigned to the following groups: normal group, CO＋saline group and CO＋hydrogen salinegroup. Hydrogen-rich saline or normal saline was given intraperitoneally in the dose of 10 mg/kg with an interval of 8 hours for six consecutive times. The normal group rats were used as normal controls. At 5 days after CO poisoning, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining, the activity of caspase-3, superoxide dismutase （SOD） and the content of malondialdehyde （MDA）, the level of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and 8-oxo-7,8-dihydro-2′deoxyguanine （8-OHdG） were conducted in established acute carbon monoxide poisoned rats. Results TUNEL-poisitive cells, the content of MDA, the level of TNF-α, IL-6 and 8-OHdG, decreased the activity of caspase-3 and SOD were apparently reduced by hydrogen-rich saline. Conclusion Hydrogen-rich saline reduced CO encephalopathy through its antioxidant, anti-apoptopic and anti-inflammatory actions.