Rationale: In mouse VEGF-C plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear. Objectives: We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants. Methods: 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia were included in the immunohistochemistry study. Tracheal aspirate fluid samples of intubated very low birth weight infants during postnatal weeks 1-5 were analyzed with ELISA. Results: Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen mostly in fetuses (8/10). Additionally, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGFR-3 staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first two postnatal days. Antenatal administration of glucocorticoids associated with higher VEGF-C in tracheal aspirate fluid. Conclusions: The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiological development of the lymphatic system of the lung.