Aims: Previous studies have reported that glucagon-like peptide-1 (GLP-1) may play a critical role in the development of intestinal ischemia-reperfusion (I/R) injury. The present study aimed to investigate whether liraglutide (GLP-1 analog) protects against intestinal I/R injury and reveals the possible underlying mechanism. Main methods: Temporary superior mesenteric artery occlusion was performed to establish an intestinal I/R injury mouse model. Different doses of liraglutide were administered in vivo. Then, the survival rate of mice exposed to different ischemia times, the histopathology, intestinal barrier index, cytokine production, intestinal tissue apoptosis, and the levels of several proteins were detected in each group. Key findings: Pretreatment with liraglutide significantly alleviated the pathological changes induced by I/R and increased the overall survival of mice exposed to intestinal I/R injury. Moreover, liraglutide attenuated neutrophil infiltration of intestinal tissues, pro-inflammatory cytokine production (including IL-1 beta, IL-6, and TNF-alpha), and apoptosis of intestinal tissues caused by intestinal I/R injury. In addition, liraglutide inhibited the nuclear translocation of nuclear factor-& UKappa;B (NF-& UKappa;B) and up-regulated the phosphorylation levels of phosphoino-sitide 3-kinase (PI3K) and protein kinase B (Akt) in the I/R group. Significance: Liraglutide may attenuate the inflammatory response and the apoptosis of intestinal tissues via the NF-& UKappa;B and PI3K/Akt pathway, protecting against intestinal I/R.