The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. As RAGE acts as cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function using a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult and old RAGE knock out (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability and inflammatory parameters (TNF-β, HMGB-1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or co-cultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.