Objective：To investigate protectory effects and possible mechanisms of lipoxin A4（LXA4）on the type Ⅱ alveolar epithelial cell line MLE-12 with hyperoxia injury. Methods：MLE-12 cells were cultured and divided into five groups randomly：I：air group，Ⅱ：hyperoxia group，Ⅲ：hyperoxia+ LXA4 group，Ⅳ：hyperoxia+ TGF-β1 neutralizing antibodies，Ⅴ：hyperoxia+ TGF-β1 neutralizing antibodies+ LXA4. The growth state and morphological changes of the cells were observed by the inverted phase microscope；the mRNA expression of collagen Ⅰ，tenascin-C，TGF-β1 receptor（TGF-βR1），TGF-βR2 and Smad3 were measured by real-time quantitative PCR；the protein levels of TGF-β1/Smads signaling pathway（TGFβR1，Smad2，Smad3，Smad4，p-Smad2 and p-Smad3）were detected by Western blot. Results：①Morphological change：the cells under hyperoxia lost their normal shapes and showed necrosis，while the cells cultured with LXA4 and/lor TGF-β1 neutralizing antibodies were normal appropriately. ②The mRNA expression of extracellular matrix（ECM）：LXA4 and TGF-β1 neutralizing antibodies attenuated the mRNA expression of collagenⅠ，tenascin-C markedly（P < 0.05），which expressed in the group hyperoxia+TGF-β1 neutralizing antibodies + LXA4 decreased most obviously. ③The mRNA and protein levels of TGF-β1/Smads signaling pathway：Compared with that of the hyperoxia group，the mRNA expression of TGF-βR1，TGF-βR2 and Smad3 decreased（P < 0.05），while the protein level of TGF-β1/Smads signaling pathway had the same change in intervention group，and it in the the group hyperoxia+ TGF-β1 neutralizing antibodies +LXA4 decreased most obviously（P < 0.05）. Conclusion：LXA4 can achieve protection of hy-peroxia-induced injury to MLE-12 which may be related to collagenⅠ， tenascin-C and TGF-β1 /Smads signaling pathway.