Objective To study the effects of hyperoxia on ventilator-induced lung injury（VILI） in rats.Methods 48 healthy male SD rats were randomly divided into four groups：Group A received conventional mechanical ventilation（VT=8 mL/kg） with room air，Group B received the same tidal volume as group A with 100% O2，Group C received large tidal volume（VT=40 mL/kg） with room air，group D received the same tidal volume as group C with 100% O2.Arterial blood gases were measured every one hour and oxygenation index（PaO2/FiO2） was calculated.The changes of lung histopathology were assessed by HE staining and observed under light microscope.Wet-to-dry weight ratio（W/D） of left lung，neutrophils and white blood cell（WBC） counts in BALF were measured.TNF-α，IL-1β，and MIP-2 levels in BALF，malondialdehyde（MDA），myeloperoxidase（MPO），and superoxide dismutase（SOD） levels in the lung were assayed，respectively.Results Compared with the Group C，the Group D demonstrated more infiltrating neutrophils in the lung and more destructive changes in the alveolar wall.Meanwhile，the oxygenation index decreased，the WBC and neutrophils counts in BALF increased，and the W/D of left lung was higher in the Group D with significant differences compared with the Group C.Moreover，the BALF levels of TNF-α，IL-1β and MIP-2，the lung levels of MDA increased，and the lung levels of SOD decreased significantly in the Group D compared with those in the Group C.There were no statistical significant differences between the Group B and Group A in all parameters except that MDA levels increased and SOD levels decreased significantly in the Group B.Conclusion Hyperoxia can increase lung injury induced in large tidal volume ventilation in rats，but has mininmal effects in conventional mechanical ventilation.