Objective To investigate the effects of sevoflurane pretreatment on Lipopolysaccharide (LPS)-induced acute lung injury(ALI) in rats. Methods Seventy-two Sprague-Dawley rats were randomly divided into 6 groups: NS group, LPS group and sevoflurane pretreatment(S-1 h group, S-6 h group, S-12 h group and S-24 h group). The rat model of ALI was established by intratracheal instillation of LPS. Animals were sacrificed at 6 h after LPS or NS administration. Leukocyte count, concentration of TNF-α and IL-1β in bronchoalveolar lavage fluid(BALF); pulmonary capillary permeability, myeloperoxidase(MPO) activity of lung tissue; lung histological changes were compared in rats with or without sevoflurane pretreatment (2.4% inspired for 30 min) at different times before LPS instillation. Results Compared with the NS group，severe injury of lung tissues and increase in leukocyte count in BALF, Production of TNF-α and IL-1β in BALF, pulmonary capillary permeability and MPO activity in the lung were significantly increased in rats treated with LPS（P<0.01）. MPO activity, leukocyte count and production of IL-1β in BALF were reduced when sevoflurane was given 1 or 24 h before but not at 6 or 12 h before LPS instillation（P<0.01）. Sevoflurane pretreatment also attenuated pulmonary capillary permeability and production of TNF-α in BALF（P<0.01）. Pulmonary capillary permeability and concentration of TNF-α in S-1 h and S-24 h group was lower than S-6 h and S-12 h group（P<0.01）. Sevoflurane pretreatment was effective at 1 h and 24 h suggesting sevoflurane has early and late protection against LPS-induced lung injury. Conclusion Sevoflurane pretreatment has protective effects against acute lung injury when given 1 or 12 h before LPS instillation.