Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is associated with decreased aquaporin-5 (AQP5) expression. Lipopolysaccharides (LPS) can decrease AQP5 expression. The effects and mechanisms of lidocaine pretreatment on primary alveolar epithelium type II (AEC II) cells injured by LPS were investigated. Primary AEC II cells were isolated from rats previously injured with LPS as an ALI model. The groups of cells were evaluated: 1) pretreated with lidocaine (2, 20, 200μg/ml) and/or Infliximab, an anti-TNF-α neutralizing antibody, 2) uninjured cells; 3) solvent pretreated injured cells and 4) untreated injured cells as controls. TNF-α levels were evaluated by ELISA. AQP5 expression was determined by mRNA and protein expression (q-PCR and western blot).The release of TNF-α was increased significantly in AEC II cells following LPS injury. The release of TNF-α was decreased by 33%-100% as a result of lidocaine pretreatment in a dose-dependent fashion. This decrease was accompanied by up-regulated AQP5 expression in LPS injured AEC II cells, and Infliximab can greatly block AQP5 expression in LPS injured AEC II cells pretreated with lidocaine. Lidocaine pretreatment (2-200μg/ml) of LPS injured AEC II cells results in a decrease in TNF-α release, then up-regulates AQP5 expression, which maybe involved in the mechanism of its effects on AEC II cells injured by LPS.