Abstract： Objective To investigate the effect and safety of positive end-expiratory pressure ventilation (PEEP)coupled with sustained inflation (SI) in the treatment of acute lung injury induced by seawater drowning in rabbits. Methods Forty-two New Zealand rabbits with acute lung injury induced by seawater drowning were treated with lower tidal ventilation coupled with positive end - expiratory pressure ventilation. During sustained inflation, blood gas, pulmodynamics, hemodynamics and lung injury weremonitored at various time points for evaluation of safety and its therapeutic effects. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) extracted from serum were also measured following treatment. Pulmonary high-resolution chromatography (HRCT) was made after 3 hours of ventilation. Then, rabbits of both groups were sacrificed for pathological examination. Results Blood gas analysis showed that the partial pressure of arterial oxygen (PaO2) at various time points increased significantly (P < 0. 05), following treatment of the animals with acute lung injury induced by seawater drowning. Lung compliance also increased with statistical significance(P < 0.05). No significant deterioration was noted in both pulmodynamics and hemodynamics.Photographic examination indicated that intrapulmonary exudation absorbed markedly. Conclusions Positive end-expiratory pressure ventilation combined with sustained inflation could significantly improve gas exchange and lung compliance, and it might be a safe and effective method for the treatment of animals with acute lung injury induced by seawater drowning.