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AIM: To study the function of interferon regulatory factor 4 (IRF4) in the lung development of bronchopulmonary dysplasia (BPD) model mice by analyzing the interaction of IRF4 and forkhead box P3 (FOXP3) and their relevance with the proliferation of pulmonary vascular endothelial cells (PVECs). METHODS: The BPD model of C57BL/6 mice exposed to 85% hyperoxia was built, and the mice in normoxia group were used as normal control. These mice were randomly divided into normoxia for 7 d (N7) group, hyperoxia for 7 d (H7) group, normoxia for 14 d (N14) group and hyperoxia for 14 d (H14) group. The lung tissue was obtained at 7 and 14 d after exposure to normoxia or hyperoxia, and the pathological changes of lung tissues were observed by hematoxylin-eosin staining. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a proliferative marker of PVECs, was detected by immunohistochemical staining. Western blot was used to detect the protein expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-1 (Ang-1), FOXP3 and IRF4. The interaction of IRF4 and FOXP3 proteins was detected by co-immunoprecipitation. RESULTS: Compared with normoxia group simultaneously, the average optical density of CD31 positive cells and the density of pulmonary vessels in hyperoxia group were significantly decreased (P<0. 01). The expression of VEGFA, Ang-1 and FOXP3 proteins in the lung tissue of mice in hyperoxia group was substantially reduced (P< 0. 01). Co-immunocoprecipitation showed that there was association between IRF4 and FOXP3, and the correlation of hyperoxia group was significantly enhanced compared with the normoxia group (P<0. 01). The expression of IRF4 and FOXP3 protein was significantly negatively correlated (R=−0. 932, P<0. 01), and the expression of FOXP3 protein was substantially positively correlated with CD31 (R=0. 865, P<0. 01). CONCLUSION: IRF4 may impact the proliferation of PVECs and the development of pulmonary vessels by inhibiting the expression of FOXP3 protein in the hyperoxia-induced BPD model mice. [ABSTRACT FROM AUTHOR]