Objective: High-mobility group box-1 (HMGB1) is a potent inflammatory mediator and contributes to acute lung injury in adults. The role of HMGB1 in neonatal lung injury and the development of bronchopulmonary dysplasia (BPD) is unknown. We studied the association between HMGB1 levels in tracheal aspirates (TAs) and adverse outcomes (BPD/death) in ventilated premature infants (VPIs) and modulation of HMGB1 levels with dexamethasone (Dex) use.Study Design: Infants born before 32 weeks gestation and requiring mechanical ventilation were enrolled. Serial TA samples were collected on days 1, 3, 5 and 7 and HMGB1 levels were measured. HMGB1 levels in TA samples were compared between infants with no BPD and infants who developed BPD or died. HMGB1 TA levels were also compared before and after using Dex.Result: In all, 24 infants (gestational age 26.4±1.9 weeks, birth weight 859 ± 200 g) had no BPD, 60 infants (gestational age 25.4 ± 1.8 weeks, birth weight 749±156 g) developed BPD or died before 36 weeks postmenstrual age. Mean HMGB1 level in first week of life was significantly lower in infants with no BPD (27.3±16.5 ng mg -1 ) compared with those who developed BPD or died (45.1 ± 30.9 ng mg -1 , P ¼ 0.004). In total, 29 VPIs received Dex. There was no significant change in HMGB1 levels with steroid therapy (before 47.0 ± 43.9, after 60.1.5 ± 58.8, P ¼ 0.3).Conclusion: Our data suggest that higher HMGB1 levels in TA are associated with the development of BPD or death in VPI. Dex use had no effect on HMGB1 levels.