Objective To study the protective effect and mechanism of action of sevoflurane on the acute lunginjury in rabbits with one-lung ventilation. Methods Thirty-six rabbits were randomly divided into three groups: shamoperationgroup, one-lung ventilation group, and one-lung ventilation + sevoflurane group. The sevoflurane concentration inthe one-lung ventilation + sevoflurane group was varied to create several subgroups. The level of arachidonic acid in lungtissue of rabbits was determined by ELISA, and the W/ D value of lung was measured. The morphological changes of lungtissue were examined pathology. The expression levels of Clara cell secretory protein ( CCSP ) and cytoplasmicphospholipase A₂ (C-PLA₂) mRNA in the lung tissue were determined by RT-qPCR. The expression levels of CCSP andC-PLA₂ protein in lung tissue were detected by western blotting. Results The level of arachidonic acid, the degree of lunginjury, and the expression of C-PLA₂ protein and mRNA in the lung tissue of the one-lung ventilation group weresignificantly higher than those of the sham operation group ( P < 0. 05), while the expression levels of CCSP protein andmRNA were significantly lower ( P < 0. 05). Arachidonic acid, lung injury, C-PLA₂ protein, and mRNA expression in thelung tissue of rabbits in the one-lung ventilation + sevoflurane group were lower than those in the one-lung ventilation group( P < 0. 05), while CCSP protein and mRNA expression levels were increased. The level of arachidonic acid, the degree oflung injury, and the expression of C-PLA₂ protein and mRNA in lung tissue of the one-lung ventilation + sevoflurane groupwere decreased with increasing sevoflurane concentration ( P < 0. 05), but there were no significant differences in theexpression of CCSP protein and mRNA. Conclusions The protective mechanism of sevoflurane against lung injury inducedby one-lung ventilation may be related to downregulation of the C-PLA₂ pathway and reduction of arachidonic acid production in the lung tissue.