The lung is constantly exposed to both environmental and microbial challenge. As a “contained” organ, it also constitutes an excellent “self-contained” tissue to examine inflammatory responses and cellular infiltration into a diseased organ. Influenza A virus (IAV) causes both mild and severe inflammation that is strain specific following infection of the lung epithelium that spreads to other cells of the lung environment. Here, we describe a method of intranasal inoculation of the lung with IAV that can be used as a preclinical model of infection. Mice can be monitored for clinical signs of infection and tissue and lung fluid collected for further analysis to dissect the immunological consequences of IAV infection. Importantly, this method can be modified to introduce other pathogens, therapies and environmental stimuli to examine immune responses in the lung.