Objectives: Neutrophils are crucial in the development of acute lung injuries during cardiopulmonary bypass. However, the efficacy of leukocyte depletion on pulmonary protection remains controversial, possibly owing to different filtration strategies used in the literature. In this study, we investigated whether short-term leukocyte depletion strategy is more efficacious than prolonged leukocyte depletion in preserving pulmonary function. Methods: Eighteen adult dogs were randomized equally into 3 groups. Leukocyte-depleting filters were used for 10 minutes in the LD-S group, throughout cardiopulmonary bypass in the LD-T group, and not used in the control group. Neutrophil counts, elastase, and interleukin-8 concentrations in plasma, myeloperoxidase and interleukin-8 concentrations in pulmonary tissue, and pulmonary vascular resistance and oxygen index were determined to evaluate the inflammatory response and damage to pulmonary function. Results: Although the neutrophil count and pulmonary parenchymal myeloperoxidase contents were significantly lower in both LD-S and LD-T groups than that in the control group, lower pulmonary parenchymal interleukin-8 level, lower pulmonary vascular resistance (113 ± 33 dyne · s/cm⁵), higher oxygen index (366 ± 82.3 mm Hg), and thinner alveolus wall thickness were seen only in the LD-S group, and the pulmonary parenchymal interleukin-8 levels were also lower in the LD-S group after cardiopulmonary bypass. The plasma elastase and interleukin-8 levels were significantly lower in the LD-S group, but they were significantly higher in the LD-T group compared with the control group after cardiopulmonary bypass. Conclusions: Short-term rather than prolonged leukocyte depletion during cardiopulmonary bypass appears to be more efficacious in protecting pulmonary function via attenuation of the extracorporeal circulation-induced inflammatory response. Crown Copyright © 2009.