We hypothesized that imbalance of proinflammatory cytokines and growth factors (GFs) in immature lungs of early postnatal life may be affected by protective ventilation strategy, and evaluated correlations of these aspects. Preterm neonate piglets were mechanically ventilated with low tidal volume and 5-6 or 10-12 cm H2O positive end-expiratory pressure (PEEP) with or without surfactant and inhaled nitric oxide (iNO) for 6 h, followed by biochemical, biophysical, and histopathological assessment of lung injury severity. Compared with surfactant and the control, iNO combined with lower PEEP exerted better oxygenation, lower activity of myeloperoxidase, lower expression of mRNA of interleukin (IL)-1beta, IL-6, IL-8, and platelet derived growth factor-B (PDGF-B), but higher expression of insulin-like growth factor-I (IGF-I), whereas that of tumor necrosis factor-alpha, keratinocyte GF, hepatocyte GF, vascular endothelial growth factor, and TGF-beta1 had no or modest changes. IL-1beta, IL-6 mRNA were closely correlated to PDGF-B mRNA and myeloperoxidase, but inversely to IGF-I mRNA, Pao2/FiO2 and dynamic lung compliance at 6 h. These results indicate that the association of lower PEEP and iNO may be more protective than surfactant on preventing lung injury and facilitating reparation by affecting the expression of proinflammatory cytokines and GFs.