Objective To investigate the molecular mechanism of Notch signaling regulating autophagy in alveolar type Ⅱ epithelial cell infected with Klebsiella pneumoniae. Methods A549 cell model of Klebsiella pneumoniae-infected human alveolar type Ⅱ epithelial cell (ACEⅡ) was constructed. The autophagy inhibitor 3-Methyladenine (3-MA) and γ-secretase inhibitor (DAPT) were used to act on A549 cells at 24, 48 and 72 hours. Real-time fluorescent quantitative PCR was used to detect the mRNA expression of autophagy-related genes LC3 and Notch signal pathway Notch1. Western blot was used to detect the protein expressions of LC3 and Notch1. ELISA was used to detect the levels of INF-γ, TNF-α and IL-1β in the cell supernatant. Results The expressions of Notch1 and autophagy-related protein LC3 in A549 cell model of Klebsiella pneumoniae-infected human alveolar type Ⅱ epithelial cell were significantly up-regulated, and the production of inflammatory factors (IL-1β, TNF-α and INF-γ) was promoted at the 24, 48 and 72 hours after infection. The inhibition of autophagy by 3-MA could down-regulate the expressions of autophagy-related proteins LC3 and Notch1 and the production of inflammatory cytokines in the cells, while the inhibition of Notch signal by DAPT could down-regulate the expressions of Notch1 and LC3 and the production of inflammatory cytokines. Conclusion Notch signal could be activated and autophagy could be induced in alveolar type Ⅱ epithelial cells infected with Klebsiella pneumoniae. The autophagy-related proteins LC3 and Notch1 in the cells may exhibit similar change trend in both transcription and protein expression levels. Autophagy and Notch signal play an important role in alveolar type Ⅱ epithelial cells infected with Klebsiella pneumoniae.