The acute respiratory distress syndrome (ARDS) is a devastating illness characterized by severe hypoxemia and diffuse alveolar damage. Direct lung infection is the leading cause of ARDS and can be modeled in mice using sterile models of inflammation or live pathogens. In this chapter, two mouse models for ARDS are defined. These include an infectious model of ARDS driven by direct administration of Streptococcus pneumoniae and a sterile inflammatory model mediated by intratracheal administration of lipopolysaccharide. Methods for growth and preparation of Streptococcus pneumoniae are provided as methods to assess lung inflammation and injury.