The transmembrane receptor (RAGE) of advanced glycation endproducts (AGEs), is abundantly present in the lung. Although the interaction of AGEs and RAGE plays an important role in vasculopathies, particularly in diabetes, the lung is not a classical target organ of diabetes. Thus, the role of RAGE in the lung is still obscure. This study sought to precisely localise RAGE in the lungs of rat and human by immunohistochemistry, double immunofluorescence and immunoelectron microscopy using a polyclonal antiserum developed against human recombinant RAGE. Anti-RAGE immunoreactivity was prominent in alveolar epithelial type I pneumocytes, while it was absent from type II pneumocytes and capillary endothelium. Cell type specificity was demonstrated by colocalisation with well established cell markers. Quantitative immunoelectron microscopy of cryo-substituted, Lowicryl-embedded rat and human specimens demonstrated a unique labelling pattern of RAGE in that it selectively localised to the basal cell membrane of type I pneumocytes. Labelling pattern was independent of the mode of fixation. Equivalent labelling densities were calculated from a fibrotic rat lung 3 months after irradiation. This highly selective localisation of RAGE to the basal face of type I pneumocytes and its absence from capillary endothelium might explain the resistance of the lung to typical diabetic complications.