The actions of RvD1 in our model of hyperoxia-induced lung injury is consistent with results by Rogers et al., whereby increasing pup exposure to DHA via supplemented dams led to improvement in inflammation but no change in the characteristic alveolar simplification seen with hyperoxia. Similar to RvD1, LXA4 demonstrated a reduction in septal wall thickening with values similar to that of the lungs in healthy, normoxia mice. However, unique to LXA4 was the improvement in alveogenesis with a reduction in MLI and increase in RAC approaching those seen in the Room Air group. The selective change in gene expression induced by LXA4 that may account for this morphometric difference between the two groups is the increase in expression of TGFb2 and to a lesser degree, the increase in Smad3. It is possible that this change in TGFb2 at the gene and protein level is unrelated to the improvement of alveologenesis observed with LXA4. However, TGFb has been described to have an important role across the spectrum of alveolar development including preservation of normal alveologenesis, as described above. Whether an increase at the protein level of Smad3 occurs with LXA4 needs to be studied further to corroborate the trends observed in gene expression. In summary, this study identified several candidate pathways by which fatty acid derived terminal metabolites may attenuate hyperoxia-induced lung injury. These pathways include their wellestablished role in regulating inflammation, but also include novel pathways in modulating the extracellular matrix and activating TGFb2-Smad3. Additional interrogation of these pathways, across different doses and including identification of the cell types involved in these pathways, are important next steps. In addition, it is important to note that in adult models of acute lung injury other pathways of attenuation have been identified with the use of these agents emphasizing their pleiotropic effects. The current study has several important implications. This is the first paper to demonstrate the role and potential pathways by which long chain polyunsaturated fatty acid derived terminal metabolites ameliorate a common neonatal morbidity that is characterized by both dysregulated inflammation and altered organogenesis. Second, it begins to offer biologic plausibility to the clinical studies documenting a relationship between systemic DHA levels and the risk of BPD. Lastly, this is the first description of the role of RvD1 and LXA4 in modulating neonatal organogenesis. The deficits in systemic levels DHA and AA, as observed in the early postnatal period in the preterm infant, potentially would also lead to lower availability of RvD1 and LXA4. Thus, strategies to replete DHA and AA during the early postnatal period of the preterm infant and/or administration of RvD1 and LXA4 may represent potential therapeutic strategies to ameliorate the development of BPD.