Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in pediatric patients. Our goal was to obtain a detailed understanding of the molecular pathogenesis of RSV infections by studying the protein expression profiles in rats with pneumonia. First, we successfully established a pneumonia rat model by intranasally injecting RSV. The differentially expressed proteins in lung tissues of RSV-infected rats compared with those of the controls were analyzed by using 2-dimensional fluorescence difference gel electrophoresis and MALDI-TOF/TOF MS. In total. 41 differentially expressed protein spots representing 20 unique proteins were successfully identified. Classification analysis showed that most of these proteins are implicated in metabolic processes, cellular processes, cellular component organization or biogenesis, and immune system processes. The significantly elevated expressions levels of 4 proteins namely, T-kininogen 1, T-kininogen 2, haptoglobin, and hemopexin, which might serve as the potential biomarkers of RSV-infected pneumonia, were further validated in RSV-infected rats using western blot and immunohistochemistry. These results provide new insights into the pathogenesis of RSV infection-induced pneumonia and provide important future directions for functional studies and therapeutic design.