Mechanical ventilation is life-saving but may evoke ventilator-induced lung injury.To explore how the circadian clock modulates severity of murine ventilator-induced lung injury via the core clock component BMAL1 in myeloid cells.Myeloid cell BMAL1-deficient (In diurnal experiments, mice ventilated at dawn exhibited higher permeability and neutrophil recruitment compared to dusk. Experiments at circadian time showed deterioration of pulmonary function, worsening of oxygenation and increased mortality at circadian time 0 compared to circadian time 12. Wild type neutrophils isolated at dawn showed higher activation and ROS production compared to dusk, while these day-night differences were dampened inInflammatory response and lung barrier dysfunction upon mechanical ventilation exhibit diurnal variations, regulated by the circadian clock.