This study aims to explore the effect and underlying mechanism of trehalose on bleomycin-induced the senescence of alveolar epithelial cells. Bleomycin was used to induce senescence in human alveolar epithelial-like A549 cells. The degree of senescence in A549 cells, induced by bleomycin with or without trehalose was determined via Western blot and senescence-associated β-galactosidase staining. Trehalose was used in combination with the autophagy inhibitors 3-methyladenine or chloroquine, and Western blot was used to detect changes in marker proteins of cellular senescence. Additionally, Western blot was used to determine the effects of trehalose on the plasminogen activator inhibitor-1 (PAI-1)/P53 pathway. The results demonstrated that trehalose alleviated the senescence of alveolar epithelial cells, and increased the levels of LC3II in alveolar epithelial cells. Inhibition of autophagy did not reverse the trehalose-induced improvement in alveolar epithelial cell senescence. Trehalose downregulated the expression levels of PAI-1 and P53 in bleomycin-treated alveolar epithelial cells. In conclusion, trehalose alleviated the senescence of alveolar epithelial cells, which was related to the downregulation of PAI-1/P53 pathway but not to autophagy activation induced by trehalose.