To investigate the molecular mechanism underlying the interaction between autophagosomes of alveolar type II epithelial (A549) cells and Klebsiella pneumoniae, an in vitro model of K. pneumoniae-infected A549 cells was established. Western blot analysis and immunofluorescence staining were used to detect the distribution of microtubule-associated protein 1A/1B-light chain 3 (LC3) and the expression of the LC3-phosphatidylethanolamine conjugate (LC3-II). K. pneumoniae-infected A549 cells were treated with different concentrations of an autophagy inhibitor or promoter for different time periods to assess the level of autophagy. Western blot analysis and immunofluorescence staining showed that K. pneumoniae could induce autophagy by A549 cells. With an increase in bacterial concentration and time of infection, autophagy gradually increased. The autophagy inhibitor significantly downregulated, while the promoter upregulated, expression of the autophagy-related protein LC3-II. Autophagy plays an important role in the resistance of alveolar type II epithelial (A549) cells to K. pneumoniae infection.