Abstract: BACKGROUND:This study’s aim is to evaluate lung ultrasound (LUS) efficacy in detecting opening and closing lung pressures and its correlation with the tracheal interleukin 6 (IL-6) level. METHOD:This single-blinded randomized controlled study was done at Ain Shams University Children’s Hospital neonatal intensive care units, Egypt. It consists of 44 mechanically ventilated preterm neonates with Respiratory Distress Syndrome (RDS). Initial LUS assessment was done followed by randomization to one of 2 groups; group I: 22 patients underwent LUS guided RM and group II: 22 patients underwent non-ultrasound guided RM. Tracheal IL-6 level was measured before and after RM in both groups. RESULTS: The LUS scores showed a sensitivity of 86.7%, specificity of 62.10% and accuracy of 70.45% at the cut-off point >B1 grade. After RM, there was a higher percentage of changes in mean airway pressure (p = 0.03), FiO2 (p = 0.01), PaO2/FiO2 ratio (p = 0.01), and IL-6 (p < 0.01) in group I. The duration of oxygen requirement (6 vs.13.5 days, p = 0.01), invasive ventilation (3 vs.5.5 days, p = 0.03), non-invasive ventilation (2.5 vs. 5 days, p = 0.02) and NICU stay (21.5 vs. 42.5 days, p = 0.03) were less in group I. A positive correlation is found between reaeration score and the duration of O2 requirement (p = 0.002), duration of invasive ventilation (p = 0.001), NICU length of stay (p = 0.002) and negative correlation with PaO2/FiO2 ratio before RM (p = 0.012). The best cut-off point for the reaeration score is >21 with a sensitivity of 75%, specificity of 71.43% and area under the curve of 78.1%. CONCLUSION: LUS-guided RM achieved earlier lowest FiO2, shorter O2 dependency, lesser NICU stay and marked decrease in lung inflammation by decreasing atelectotrauma and shortening the duration of invasive ventilation.