Objective To investigate the mechanisms of propofol on ventilator-induced lung injury in rats produced by high PIP ventilation. Methods Twenty-four anesthetized Wistar rats weighting 280 g -320 g were randomly divided into three groups (n = 8). Rats were ventilated with high PIP pattern (PIP=25 cm H2O，PEEP=2 cm H2O) for 4 h. Propofol was given in a bolus of 2 mg/kg (group B) or 5 mg/kg (group C), followed by continuous infusion with 4 mg•kg-1•h-1 (group B)or 10 mg•kg-1•h-1(group C). No Propofol was given for group A. MAP, HR were recorded and arterial blood gases were analyzed. Lung wet and dry weight ratio(W/D), tumor necrosis factorα(TNF-α), interleukin1β(IL-1β), IL-6, IL-10, macrophage inflammatory protein2(MIP-2) and protein content in bronchoalveolar lavage fluid (BALF) , content of malondialdehyde(MDA) and superoxide dismutase (SOD) in lung homogenate were determined. Pathological change of lung was examined and lung injury was scored as well. Results MAP and PaO2 decreased from(116.0±7.4) mm Hg and (379±65) mm Hg to (73±21)mm Hg and (103±48)mm Hg, and PaCO2 increased at fourth hour in group A(P＜0.05). PaO2 in group B and C were higher than in group A after 3 h(P＜0.05). Lung W/D weight ratio, TNF-α, MIP-2 and protein content in BALF were higher in group A(P＜0.05), and MDA was higher in group A(P＜0.05). No significant difference between group B and C. Pathological changes of lung in group B and C were all better than those in group A. Conclusion Propofol may attenuate VILI in rats partly by reducing the release of cytokine, decreasing the accumulation of neutrophil in the lung, and inhibiting peroxidized injury.