CXCR4 and acute respiratory distress syndrome: This animal model was designed to suffice key criteria of the Berlin definition of ARDS15, i.e. to result in a ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) < 300 mmHg under positive end-expiratory pressure ≥ 5 cmH2O. Our findings show that treatment with CXCR4 agonists during the early fluid resuscitation period prevents development of lung ischemia–reperfusion injury and hemorrhage induced ARDS in rats and suggest that the development of engineered CXCR4 agonists with improved therapeutic efficacy is possible.