[Abstract] Objective： To investigate the effectiveness of azithromycin (AZM) on bronchopulmonary dysplasia (BPD) in neonatal rats. Methods: Neonatal rats were randomly assigned to four groups: room air-saline (RA-Saline)group, room air-azithromycin (RA-AZM)group, oxygen-saline (O2-Saline)group, and oxygen-azithromycin (O2-AZM)group. The oxygen groups were exposed to 95% to 100% oxygen within 12 hours of birth to establish a BPD rat model. The RA-AZM and O2-AZM groups received daily intraperitoneal injections of azithromycin (AZM) at a dosage of 40 mg/kg from postnatal day 1 to day 10, while the corresponding control groups were administered an equal volume of saline. The survival rate of the rats was carefully observed. qPCR analysis was conducted to detect the expression of inflammatory factors and chemokines. Additionally, the alveolar mean linear intercept (MLI), the formation of secondary alveolar septa, and pulmonary vascular density were measured to assess the impact of AZM on lung development in BPD neonatal rats. Immunohistochemical detection of neutrophils and macrophages in lung tissue was also performed to evaluate the anti-inflammatory effect of AZM on inflammatory cells. Results: Compared to the O2-Saline group, the 10-day survival rate of rats in the O2-AZM group did not exhibit a statistically significant difference (P > 0.05). qPCR analysis revealed that the expressions of IL-6 (Interleukin-6), MCP-1 (monocyte chemotactic protein-1), and PAI-1 (plasminogen activator inhibitor-1) were significantly reduced in the O2-AZM group compared to the O2-Saline group (P < 0.05), while the expression of CINC-1 (cytokine induced neutrophil chemoattractant-1) showed no significant difference (P > 0.05). ELISA analysis further confirmed a significant reduction in IL-6 levels in the O2-AZM group compared to the O2-Saline group (P < 0.05). Immunohistochemical analysis revealed a marked reduction in the accumulation of macrophages and neutrophils in the lung tissues of the O2-AZM group, along with an increase in pulmonary vascular density and the count of secondary alveolar septa, all of which were statistically significant. Furthermore, HE pathological examination revealed a significantly shortened alveolar mean linear intercept (MLI) in the O2-AZM group compared to the O2-Saline group, indicating a statistically significant difference (P < 0.05).Conclusion: AZM reduces the release of inflammatory factors/chemokines in lung tissues of neonatal rats exposed to hyperoxia, inhibits the chemotaxis or recruitment of inflammatory cells, and alleviates BPD-like lung injury in neonatal rats after hyperoxia exposure. Key words: azithromycin; bronchopulmonary dysplasia; hyperoxia exposure; inflammation; lung development