Objective To observe the protective effects of ambroxol hydrochloride ( AMB) on rabbit model of acute lung injury ( ALI) induced by oleic acid and explore its mechanisms. Methods The ALI model of rabbit was induced by oleic acid. Twenty-four Japanese white rabbits were divided into three groups randomly, ie. a normal saline group ( NC group) , an ALI group and an ALI plus ambroxol injection group ( AMB group) . The pathological changes and apoptotic index ( AI) in lung tissue, Caspase-3 activity in lung tissue homogenate were observed 6 hours after the intervention. Serum activity of superoxide dismutase ( SOD) and serum levels of malonaldehyde ( MDA) , interleukin-1β( IL-1β) , and tumor necrosis factor-α ( TNF-α) were measured simutanously. Results The pathological injury of lung in the AMB group was milder than that in the ALI group. Both the AI in lung tissue and Caspase-3 activity in homogenate in the AMB group were lower than those in the ALI group significantly ( P lt;0. 01, P lt;0. 05 respectively) , butwere higher than those in the NC group( both P lt; 0. 01) . The activity of SOD in serum measured 6 hours after AMB intervention was higher while the serum levels of MDA, IL-1βand TNF-αin serum were lower ( P lt;0. 01) than those in the ALI group significantly ( all P lt;0. 01) . Conclusions Ambroxol hydrochloride has protective effects on oleic acid-induced acute lung injury. The mechanisms may be related to inhibition of oxidative stress and suppression of cytokines synthesis ( IL-1βand TNF-α) , the activity of the Caspase-3,and the apoptosis of lung tissue.