The aim of the present study was to investigate the potential role of dub cell secretory protein (CCSP), an endogenous modulator, in reducing pulmonary inflammation induced by sevoflurane following one-lung ventilation (OLV). Healthy Japanese white rabbits were randomly assigned to six groups: Sham-operated group (group S); respiratory management of OLV group (group O); OLV + sevoflurane treated group (group OF), club cells exfoliated + sham-operated group (group NA), dub cells exfoliated + OLV group (group NAO); and club cells exfoliated + OLV + sevoflurane treated group (group NAOF). At the end of the experimental observation, all animals in the different groups were sacrificed and lung injury was evaluated according to the lung wet/dry weight ratio and histological scoring system. Lung homogenates were harvested to detect the mRNA and protein expression of cytosolic phospholipase A2 (c-PLA(2)) and CCSP. The content of arachidonic acid was measured using an ELISA. Following OLV treatment, c-PLA(2) expression was increased, CCSP expression was decreased and lung injury scores were significantly increased. Sevoflurane inhalation in the OLV-treated group induced an upregulation of CCSP and a downregulation of c-PLA(2) expression. In the group NAO, in which the club cells were simultaneously exfoliated, OLV caused more severe lung damage and induced higher expression of c-PLA(2) compared with that in group O. However, sevoflurane inhalation reduced the extent of lung injury and the expression of c-PLA(2) even when the endogenous modulator of lung inflammation, CCSP, was exfoliated (group NAOF). These results indicated that OLV, promoted lung inflammation through the CCSP and c-PLA(2) pathway. However, the results from the club cells exfoliated group indicated that the CCSP may not be involved in the protective effect exerted by sevoflurane inhalation.