Introduction: Primary organ failure after lung transplantation is still a feared complication with a high morbidity and mortality. The primary trigger is ischemia/reperfusion injury due to insufficient organ conservation. Methods: In 2 experimental dog models, 4 test series were accomplished. The effectiveness of surfactant application and the change in pulmonary vascular resistance was investigated in a left lung transplantation model. A warm ischemia/reperfusion model was established for studying the role of ischemic preconditioning and induction of endotoxin tolerance in reperfusion injury of lungs. Results: 1. Bronchoskopic application of bovine surfactant leads to a restoration of the surfactant function and, accordingly, to an improvement in gas exchange and pulmonary compliance in the transplanted organ. The increased permeability could, however, hardly be affected. 2. Ischemic preconditioning of 5 minutes (however not 2 cycles of 10 minutes) improves lung function after warm ischemia and reperfusion significantly. 3. Mitigation of reperfusion injury after warm ischemia was obtained by pre-treatment with endotoxin. Conclusion: The inflammatory response after ischemia and reperfusion of the lung can be reduced by pre-treatment of the organ. The molecular mechanism of ischemic preconditioning or endotoxin tolerance still remains poorly understood. An improved understanding of protective mechanisms may enable the development of clinical strategies preventing reperfusion injury.