Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia (BPD) in premature infants. We have previously shown that perinatal pulmonary expression of human interleukin-1 (IL-1) is sufficient to cause a lung disease similar to BPD, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The v6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the 6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1-expressing infant mice with wildtype or null 6 integrin loci. Absence of the 6 integrin subunit decreased the mortality and improved the postnatal growth of IL-1-expressing pups. The disrupted alveolar development of IL-1-expressing mice was improved by 6 integrin deficiency. IL-1-expressing 6^-/- pups had shorter alveolar chord length and thinner alveolar walls than IL-1-expressing 6^+/+ pups. In addition, the absence of the 6 integrin subunit reduced IL-1-induced neutrophil and macrophage infiltration into the alveolar spaces. Beta6 integrin subunit deficiency suppressed inflammation and goblet cell hyperplasia in the airways and alleviated airway remodeling in IL-1-expressing mice. The expression of the chemoattractant proteins keratinocyte-derived chemokine (KC, CXCL1), macrophage-inflammatory protein (MIP)-2 (CXCL2), S100A8 (calgranulin A) and S100A9 (calgranulin B), of osteopontin, and of the chitinase-like lectins Ym1 and Ym2 was lower in IL-1-expressing 6^-/- than in IL-1-expressing 6^+/+ mice. We conclude that absence of the 6 integrin subunit protects the infant murine lung against IL-1- induced inflammation and injury.