Objective:To investigate the protective roles of lipoxin A4 (LXA4) in hyperoxia-induced bronchopulmonary dysplasia(BPD) in neonatal mice and the possible mechanisms. Methods:BPD was induced by 85% O2 exposure. C57/BL6 neonatal mice were randomized divided into the air group,the hyperoxia(85% oxygen)group,the hyperoxia +LXA4 group,and the hyperoxia + TGF-β1 antibodies (1D11) group. The weight and growth status of the mice were recorded daily. The pathologic changes of pulmonary tissues were observed by hemotoxylin and eosin (HE) staining. Not only the expression of fibrosis indexes of the lung,but also quantitative expressions of TGF-β1 receptor(TGF-βR1)and TGF-βR2 were detected by real-time quantitative PCR. Results:①Model neonatal mice under hyperoxia circumstance presented growth retardation and poor activity compared with the air controls.②Compared with the air group,decrease of volume and darkness of color were observed in pulmonary tissues of mice in the other three groups on d7. However,the colors of pulmonary tissues in the LXA4 and the 1D11 treated groups were similar with the air group on d13. ③Compared with the air group on d7,the pathology changes of other three groups were consistent with BPD. In comparison to the models on d13,treatment with LXA4 or 1D11 led to the normalization of alveolar structure.④Hyperoxia resulted in significant increase in the mRNA expressions of fibrosis indexes in the lung,such as,fibronectin,α-SMA,elastin,tenascin-C and TIMP-1. There were also overexpression of TGF-βR1 and TGF-βR2(P < 0.05). The uptrend of expression of MMP-1 was found in both the LXA4 group and the 1D11 group,which was opposite in the hyperoxia group. Furthermore,it was more notable in the mice treated with LXA4. The quantity of collagen I expression was promoted by hyperoxia exposure(P < 0.05) compared with controls. The reduction of collagen I was detected both in treatment of LXA4 and 1D11 (P < 0.05). Conclusion:LXA4 can play a protective role in hyperoxia-induced BPD in neonatal mice by reducing the expression of fibrosis indexes modulated by the signaling pathways of TGF-β1.