Objective To investigate the effects of mechanical ventilation( MV) via different tidal volume ( VT) in combination with positive end expiratory pressure( PEEP) on dogs with acute lung injury( ALI) . Methods Dog model of oleic acid-induced ALI was established. And after that animals were randomized into different MV groups ( included low VT group, VT =6 mL/kg; and high VT group, VT =20 mL/kg) and ventilated for 6 h with a PEEP of 10 cmH2O. Arterial blood gas wasmeasured before, during and after ALI model was established ( at 1 h,2 h, 4 h and 6 h during MV) . The albumin concentration in BALF and pathological change of the lung tissue were evaluated in order to determine the lung injury while animals were sacrificed after 6 h MV. Results ALI model was successfully established ( 2. 50 ±0. 80) hours after oleic acid injection. Arterial pH decreased much severer in the low VT group than the high VT group( P lt;0. 01) . PaO2 and SaO2 in ventilation groups decreased after modeling but increased after MV, and PaO2 and SaO2 were significantly higher in the low VT group than the high VT group after 6 h MV( P lt;0. 05) . PaCO2 fluctuated less in the high VT group, while it increased significantly in the low VT group after MV( P lt; 0. 01) . Oxygenation index( PaO2 /FiO2 ) was lowered after modeling( P lt; 0. 01) , decreased to about 190 mm Hg after 1 h MV. And PaO2 /FiO2 in low VT group was significantly higher than the high VT group after 6 h MV( P lt; 0. 05) . BALF albumin concentration and the lung injury score in the low VT group were both significantly lower than the high VT group( both P lt; 0. 05) . Conclusions Ventilation with PEEP could improve the oxygenation of ALI dogs, and low VT ventilation improves the oxygenation better than high VT. Otherwise, low VT could induce hypercapnia and ameliorate lung injury caused by high VT MV.