Background: Ischemia-reperfusion injury is a common complication after lung transplantation. Ischemia-reperfusion injury is thought to be mediated by reactive oxygen species (ROS). Hydrogen sulfide (H2S) is a novel agent that has been previously shown to scavenge ROS and slow metabolism. We evaluated the effect of infused H2S on the presence of ROS after reperfusion in an ex vivo model of lung transplantation. Methods: Heart-Lung blocks were recovered from New Zealand white rabbits (n = 12) and cold stored in Perfadex solution for 18 h. After storage, the heart-lung blocks were reperfused ex vivo with donor rabbit blood. In the treatment group (n = 7), a bolus of sodium H2S was added at the beginning of reperfusion (100 μg/kg) and continuously infused throughout the 2-h experiment (1 mg/kg/h). The vehicle group (n = 5) received an equivalent volume of saline. Serial airway and pulmonary artery pressures and arterial and venous blood gases were measured. Results: Oxygenation and pulmonary artery pressures were similar between the 2 groups. However, treatment with H2S resulted in a dramatic reduction in the presence of ROS after 2 h of reperfusion (4,851 ± 2,139 versus 235 ± 462 related fluorescence units/mg protein; P = 0.003). A trend was seen toward increased levels of cyclic guanosine monophosphate in the H2S-treated group (3.08 ± 1.69 versus 1.73 ± 1.41 fmol/mg tissue; P =.23). Conclusions: After prolonged ischemia, infusion of H2S during reperfusion was associated with a significant decrease in the presence of ROS, a suspected mediator of ischemia-reperfusion injury. To our knowledge, the present study represents the first reported therapeutic use of H2S in an experimental model of lung transplantation. © 2012 Elsevier Inc. All rights reserved.