Rationale: Whether the ventilator-induced tung injury (VILI) superimposed on ischemia/reperfusion injury (I/R) causes synergistic damage has not been well. explored. Whether nuclear factor-kappa B (NF-kB) antibody has protective effects for both injuries is also unknown. Methods: I/R and VILI were produced in an isolated rat lung model. Hemodynamics, lung weight gain (LWG), capillary filtration coefficient (K-fc), cytokines, and lung pathology were assessed. Results: VILI or I/R produced similar permeability pulmonary edema which was reflected by increasing K-fc and LWG. Cytokine (IL-1 beta) up-regulation occurred in both injuries. Pathologic examination showed edema and inflammatory cell. infiltration in VILI or I/R. In addition, the alveoli were overdistended and even ruptured because of marked inhomogeneity of inflation in VILI. Furthermore, combined I/R and VILI produced further increases in K-fc, LWG, IL-1 beta, as well. as more severe pathologic changes. Conversely, less permeability pulmonary edema, pathologic changes and IL-1 expression were found in groups pretreated with anti-NF-kB antibody. Conclusion: VILI and I/R cause synergistic damage on the lung. I/R or VILI alone or combined can be attenuated by NF-kB antibody. NF-kB plays an important rote in both forms of tung injury. We propose anti-NF-kB antibody pretreatment to be beneficial for VILI, I/R and tung transplantation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.