LPL is required for the generation of alveolar macrophages and supports transmigration of cells into alveoli and retention within the alveolar microenvironment. Our data suggest a model in which LPL is required for transmigration of alveolar macrophage precursors into the alveoli during development. Our data also show that LPL is required for engraftment of monocytes and/or mature alveolar macrophages into alveoli.