The data presented in this study 1) confirm that platelets are present in the alveolar space during inflammation, primarily in aggregates with neutrophils; 2) show that CLEC-2 expressed on platelets protects against excessive lung inflammation in a mouse model of ARDS; 3) are suggestive of a nonessential, or redundant, role for the CLEC-2 ligand, podoplanin, on AECI and LECs during lung development and function during inflammation; and 4) implicate podoplanin expression on hematopoietic-derived cells in protecting against exaggerated lung inflammation in a mouse model of ARDS. Here, PDPN is linked to acute respiratory distress syndrome.