Objective To investigate the role of glucagon-like peptide-1 (GLP-1) receptor in the lipopolysaccharide(LPS)-induced acute lung injury (ALI) and its mechanism. Methods ALI in rats was induced by intratracheal administration of LPS. A total of 30 rats were randomly divided into 5 groups, with 6 in each:the control group, sham model treated with normal saline (NS); the drug-blank group, sham model treated with liraglutide (2mg/kg); the model group, ALI model treated with NS; the treatment group, ALI model treated with liraglutide (2mg/kg); and the inhibitor group, ALI model treated with liraglutide (2mg/kg) and 3-methyladenine (10mg/kg). Expression of LC3II, Beclin-1, P62, Bax and Bcl-2 were detected by Western blotting. Cell apoptosis was determined by the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-Triphosphate-Digoxigenin nick end labeling (TUNEL) assay. SPSS statistics 20.0 was used for data processing, and one-way analysis of variance and LSD multiple comparisons were used for comparison between groups. Results The expression of LC3II, Beclin-1 and P62 in the model group were 100.0%±5.3%, 100.0%±5.6%, 100.0%±6.1%, respectively. The expression of LC3II and Beclin-1 in treatment group increased respectively to 214.0%±12.3% and 329.0%±33.8%, and that of P62 decreased to 50.0%±7.0% (P<0.01). The control group had a lung injury score of 0.3±0.5, a wet/dry weight ratio (W/D) of 4.08±0.14, a Bax of 100.0%±7.0%, a Bcl-2 of 100.0%±3.6%, and apoptotic cells of 1.0±0.9. In the model group, the lung injury score, wet/dry weight (W/D), expression of Bax and apoptotic cells increased respectively to 4.6±0.8,4.83±0.23,284.0%±25.6% and 42.5±8.2, and expression of Bcl-2 decreased to 63.0%±6.2% (all P<0.01). Compared with the model group, the lung injury score, W/D, expression of Bax and apoptotic cells in treatment group decreased respectively to 2.5±1.0,4.42±0.15,198.0%±24.8% and 17.0±3.4, and the expression of Bcl-2 in treatment group increased to 83.0%±5.3% (all P<0.01). Compared with the treatment group, the lung injury score, W/D, expression of Bax and apoptotic cells in inhibitor group increased respectively to 4.3±0.8, 4.77±0.25,277.0%±25.5% and 39.5±6.2, and expression of Bcl-2 in inhibitor group decreased to 54.0%±5.0% (all P<0.01). Conclusion Activation of GLP-1 receptor significantly alleviates LPS-induced ALI, and the mechanism is associated with the up-regulation of autophagy that prevents cell apoptosis.