<p><b>OBJECTIVE</b>To investigate the intervention and mechanism of ambroxol combined with low-doseheparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with acute lung injury (ALI).</p><p><b>METHODS</b>Twenty-four healthy Japaneserabbits were randomly divided into three groups (1) Normal salinecontrol group (NC), (2) Oleic acidinjury group (OA), (3) Ambroxol + low-doseheparintherapy group (AH). After the success of ALI model, AH group was injected ambroxol + low-doseheparin, while the NC group and OA group were injected the same dose of normal saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were determined. The pathological manifestation of both side lungs was observed at the end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lungtissue homogenate were tested. The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated. The pathological changes in lungtissue were observed by light microscopy, and the ultrastructural changes of lungtissue were observed by electron microscopy.</p><p><b>RESULTS</b>(1) The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group. (2) PaO2 was improved significantly in AH group, compared with that in OA group (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of MDA decreased significantly (P < 0.01), compared with those in OA group. (4) Except the content of IL-1beta in serum before treatment, the content of IL-1beta and TNF-alpha in serum, BALF, lungtissue homogenate of OA group increased significantly (P < 0.01), and those were obviously improved in AH group. (5) Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with that in OA group.</p><p><b>CONCLUSION</b>In ALI induced by OA, IL-1beta and TNF-alpha increases significantly and involved in the occurrence and development of ALI. Ambroxol combined with low-doseheparin can reduce lungcellsoxidative stress to inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment of ALI.</p>