HSR incites pulmonary inflammation that leads to acute respiratory distress syndrome (ARDS). However, there have been no definitive pharmacological therapies against ARDS. CO is a toxic gas due to the generation of carboxyhemoglobin (COHb). However, trace amount of CO is endogenously produced by the enzymatic reaction of heme oxygenase-1 (HO-1) that is induced by oxidative stress to confer protection against various inflammatory disorders. Recent studies have indicated that low dose of CO exerts potent cytoprotective effects on inflammatory organ damage in animal models by its anti-inflammatory property. We also demonstrated that CO inhalation at 250 ppm ameliorated HSR-induced pulmonary injury in rats. However, this dose of CO increased blood COHb level to approximately 20% that may be toxic to humans. Very recently, to overcome the disadvantage, CORMs have been developed by coordinating CO with a transition metal carbonyl complexes. Among various types of CORMs, CORM-3, a water-soluble CORM, spontaneously liberated and deliver CO to various tissues under physiological condition through intravenous administration. We found that CORM-3 treatment mitigated HSR-induced lung injury without any increase in blood COHb levels through its anti-inflammatory property. We propose that CO/CORMs are possible pharmacological agent to treat ARDS.