In addition, LCPUFAs are important in regulating the inflammatory response through several mechanisms. One critical pathway is through the production of docosahexaenoic acid and arachidonic acid derived terminal metabolites, such as Resolvin D1 and Lipoxin A4, respectively. Current options for the parenteral and enteral delivery of LCPUFAs are unable to meet estimated fetal accretion rates; and, as a result, there is a rapid deficit of DHA and AA levels with no recovery to birth levels during the neonatal course. Of clinical significance, this early postnatal decline in systemic DHA levels is associated with the development of BPD. Animal data support this clinical observation as well as a potential role for DHA in attenuating the risk of BPD. In a neonatal murine model of hyperoxia-induced lung injury, pups exposed to hyperoxia and supplemental DHA, either by increasing the DHA content in dam milk or by direct enteral administration, demonstrated reduced lung inflammation and increased alveolarization compared to pups exposed to hyperoxia without DHA. However maintaining birth levels of LCPUFAs, in particular DHA and AA, is not achievable with the current standard of nutritional care in the neonatal intensive care unit. Thus, in lieu of directly changing dietary DHA and AA delivery, we sought to determine whether exogenous administration of the biologically active DHA and AA derived terminal metabolites, Resolvin D1 and/or Lipoxin A4, would attenuate hyperoxia-induced lung injury and if so, to define the pathways modulated by these mediators. In a well-established neonatal model of lung injury, the administration of the bioactive terminal metabolites of DHA and AA, RvD1 and LXA4 respectively, attenuated the morphologic and cellular responses to hyperoxia-induced lung injury. In parallel, there was improvement in pup growth with the combination of RvD1/LXA4, which was principally driven by LXA4. These findings support a mechanistic role for fatty acid derived terminal metabolites in ameliorating specific pathways that contribute to severe lung disease in preterm infants. In addition, these results may explain the association of low systemic levels of DHA to an increased risk of BPD observed in clinical studies. Consistent with previous studies, we found that exposure of mice to hyperoxia in the early neonatal period disrupts normal lung development as evidenced by the morphometric changes of increased septal wall thickness and arrested alveologenesis. Also, consistent with previous studies, is the induction of the host inflammatory response with hyperoxia exposure. In our study, we demonstrated an increase in the gene expression of CXCL2, the murine equivalent of IL-8, and to a lesser extent IL1b? We did find in parallel an increase in the gene expression of TIMP1 with a concomitant decrease in the expression of ELN, LOXL2, and Col1A1.