Objectives: (a) to evaluate the effect on oxygenation and ventilation of rabbits with induced surfactant depletion when they are submitted to a conventional mechanical ventilation, plus a small dose of exogenous surfactant; (b) to compare this group with another group submitted to a High Frequency Oscillation (HFO) without exogenous surfactant administration. Methods: Twenty New Zealand White rabbits weighing (± 3 kg) were anaesthetized and artificially induced to a endogenous surfactant depletion by successively lung lavage with normal saline (aliquots of 25 ml/kg) until to reach a persistent PaO 2 less than 100 mmHg when submitted to a mechanical ventilation in a pressure control mode with a target tidal volume of 10ml/kg, PEEP of 5cm H 2O, FiO 2 1.0, respiratory rate 30/min, and inspiratory time of 0.65 s. Then the rabbits were divided in (a) CMV+S group, submitted to a conventional mechanical ventilation plus exogenous surfactant replacement; (b) HFO group, submitted to a High Frequency Oscillation Ventilation. Arterial blood gases were measured at control period, post lung lavage, 15, 16 and 120 minutes after treatment started. The groups were compared using Student t test. Results: The post lung lavage PaO 2 in both groups was lower than 50mmHg (p = 0.154), increasing after 15 min of treatment to 254 mmHg (CMV+S) and 288 mmHg (HFO, p = 0.626). The PaO 2 at 60 and 120 minutes were higher (p = 0.001) in the HFO group (431 e 431 mmHg) when compared with the CMV+S group, which showed a progressive fall (148 e 126 mmHg). At 60 minutes of treatment, the PaCO 2 was lower (p = 0.008) in the CMV+S group (29 versus 41 mmHg). Conclusions: In ARDS animal model a protect mechanical ventilation strategy as HFO by itself promotes a fast and persistent increase in the oxygenation, with superior levels than those observed in animals treated with conventional mechanical ventilation plus exogenous surfactant replacement.