Silent mating type information regulation 2 homolog-1 (SIRT1) is involved in a wide range of cellular processes because of its role as a deacetylated histone and its association with a variety of transcription factors. SIRT1 has essential roles in autophagy, including in the formation of autophagic vacuoles and the assembly of autophagy-related gene (ATG) protein complexes. The present study focused on the role of SIRT1 in autophagy in lipopolysaccharide (LPS)-induced mouse type II alveolar epithelial cells (AECII). We designed experiments using SIRT1-overexpressing mice and wild-type mice, and AECII were isolated from these two types of mouse for in vitro LPS injury trials. Our results suggest that levels of the autophagy proteins, Beclin1 and LC3B, as well as those of the inflammatory factors, IL-6 and TNF-α, were increased in LPS-induced mouse AECII, and that SIRT1 protected against damage in mice with acute respiratory distress syndrome and in mouse AECII in vitro following LPS treatment. Subsequently, we screened multiple inflammatory, apoptotic, and unclassified genes (including Atg7), which interacted with SIRT1 in LPS-injured mouse AECII, as assessed by mRNA microarray analysis. These results demonstrate that LPS can reduce the levels of SIRT1 and ATG7 in vivo and in vitro and indicate that SIRT1 is involved in autophagy through regulation of ATG7 in AECII in response to LPS.