OBJECTIVE: To investigate the expression of caveolin-1 (cav-1) and its downstream signal under mechanical ventilation with different tidal volumes (VT) in lung tissue of rats. METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly assigned into five groups (each n=8). The rats in control group (group A) remained to have spontaneous breathing but underwent tracheostomy only. The rats in protective ventilation group underwent protective ventilation for 1 hour or 2 hours (group B1, B2), with VT set at 6 ml/kg. The rats in high VT ventilation group were given mechanical ventilation for 1 hour or 2 hours (group C1, C2), with VT set at 30 ml/kg. After incision of trachea in group A, and mechanical ventilation was given for 1 hour or 2 hours in ventilation groups. Rats of group A were sacrificed immediately. Rats of other groups were sacrificed 1 hour or 2 hours after mechanical ventilation. Specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Lung pathological changes were observed with optical microscope. The expression levels of cav-1 mRNA and eNOS mRNA in lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cav-1, endothelial nitric oxide synthase (eNOS), interleukin-1 receptor-associated kinase 4 (IRAK4) and nuclear factor-ΚB (NF-ΚB) p65 in lung tissues were assayed with immunohistochemistry staining. Lung myeloperoxidase (MPO) activity was measured by colorimetric analysis, and wet/dry weight ratio (W/D) was calculated. The levels of tumor necrosis factor-α (TNF-α) in BALF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: No statistical significance in the mRNA expression of cav-1 and eNOS, the protein expression of cav-1, eNOS, IRAK4, NF-ΚBp65, as well as W/D ratio, MPO and TNF-α in BALF was found among group A, group B1 and group B2. The expression of cav-1 mRNA (A value ratio) and cav-1, IRAK4, NF-ΚBp65 protein (A value) were significantly up-regulated (cav-1 mRNA: 0.833±0.085 vs. 0.384±0.011, 1.162±0.166 vs. 0.388±0.014; cav-1 protein: 0.188±0.011 vs. 0.140±0.052, 0.210±0.013 vs. 0.125±0.014; IRAK4 protein: 0.181±0.009 vs. 0.150±0.008, 0.205±0.085 vs. 0.155±0.012;NF-ΚBp65 protein: 0.294±0.011 vs. 0.236±0.015, 0.304±0.012 vs. 0.239±0.005), the expression of eNOS mRNA (A value ratio) and protein (A value) was significantly down-regulated (eNOS mRNA: 0.174±0.016 vs. 0.278±0.021, 0.107±0.014 vs. 0.262±0.045; eNOS protein: 0.180±0.017 vs. 0.211±0.010, 0.161±0.016 vs. 0.216±0.013), while W/D ratio, MPO and TNF-α in BALF were significantly increased (W/D: 5.64±0.42 vs. 4.63±0.12, 6.73±0.83 vs. 4.70±0.15; MPO: 1.86±0.26 U/g vs. 0.85±0.11 U/g, 2.14±0.24 U/g vs. 0.88±0.18 U/g; TNF-α: 386.53±29.12 ng/L vs. 50.57±10.98 ng/L, 455.77±37.78 ng/L vs. 52.11±9.92 ng/L) in group C1 and group C2 compared with those in group B1 and group B2 (all P<0.05). With prolongation of time of mechanical ventilation, changes in those parameters were more obvious in group C2 as compared with group C1 (all P<0.05). CONCLUSION: Cav-1 and the activation of downstream signals in lung tissue participate in the development of the ventilator-induced lung injury.