Influenza A virus (IAV) infection causes an inflammatory reaction and activation of coagulation, which is often the basis for destruction of lung tissue. This study examines the changes to the of lungs from IAV-infected mice and assesses the effectiveness of Argatroban, a thrombin inhibitor, when given early in the infection. Pro-inflammatory and cell adhesion proteins were significantly upregulated in lung tissue on the first day after infection. As disease progressed, proteins related to coagulation, immunological signaling, and oxidative stress were more highly expressed in infected lungs. Argatroban treatment notably shifted the proteomic response on Day 1 and Day 5 post- infection, pointing to the ability of argatroban to control oxidative and inflammatory reactions during IAV infection, which may have consequences for maintaining lung function and reducing tissue damage brought on by the virus.