The aim of this study is to investigate the protective effect and underlying mechanism of antitumor necrosis factor- antibody (TNF- Ab) on lung tissue injury after cardiopulmonary bypass (CPB). Twenty-eight healthy New Zealand white rabbits were randomly divided into four groups. Group I received only an open chest operation. Groups IIIV all received CPB. Furthermore, groups III and IV received post-CPB endotracheal intubation with phosphate buffered saline or TNF- Ab (2400pg/kg), respectively. Perioperative blood neutrophil count, TNF- level, and malondialdehyde (MDA) levels were determined in both the right and left atriums. Lung water content, TNF- messenger RNA, protein, apoptosis in situ, and pathomorphological changes were also measured. The results show that TNF- Ab can significantly inhibit leukocyte accumulation, reduce secretion of TNF- and MDA, decrease lung tissue apoptosis, and attenuate post-CPB pathomorphological changes. TNF- Ab administration, however, cannot suppress the expression of TNF-, suggesting that the protective effects of TNF- Ab originate from inhibiting the numerous biological functions of TNF-. Intratracheal TNF- Ab administration demonstrates a notable protective effect against lung injury after CPB.