Introduction: The polarization of T helper (Th) cells plays an important role in the inflammatory response, pathogen removal, and tissue damage processes of infectious acute lung injury (ALI). However, Th cell polarization in viral- or bacterial-mediated ALT is not well defined. Herein, an influenza virus (A/FM/1/47, H1N1) and lipopolysaccharide (LPS) were chosen to induce ALI in mice, and the resultant diversity of Th-cell polarization was explored. Methodology: BALB/c mice were challenged intranasally with the influenza virus or LPS. Edema of the lung, infiltration of inflanunatoiy cells (macrophages, neutrophils, and lymphocytes), oxidative stress, and signature cytokines of Th1 and Th2 cells were detected at 2 days post virus or LPS challenge. Results: The mice exhibited increased capillary permeability accompanied by lung edema and protein-rich alveolar exudation after virus or LPS challenge. Additionally, excessive infiltration of inflammatory cells, robust oxidative stress, and cytokine production were observed in both mouse groups. However, there was conspicuous disparity in the inflammatory cell infiltration and cytokines between the virus- and LPS-challenged mice, where the infiltration in virus-challenged mice was mainly of macrophages and accompanied by robust Th1 cytokine elevation, whereas the infiltration in LPS-challenged mice was primarily of neutrophils and accompanied by robust Th2 cytokine elevation. Conclusions: The Th cell polarization was skewed depending on whether ALI was induced by the influenza virus or LPS. The polarization in the virus-challenged mice was primarily toward a Th1 response, whereas that in the LPS-challenged mice was mainly toward Th2.