Aim To investigate the effects of liraglutide on cholesterol efflux in HepG2 cells under high glucose condition, and to detect the expression of related protein and further to explore its mechanism of action. Methods HepG2 cells were cultured in vitro, stimulating with high glucose and intervening with different concentrations of liraglutide.Effect of liraglutide on cholesterol efflux in HepG2 cells under high glucose condition was detected by using BODIPY-cholesterol fluorescence assay. Western blot was used to analyze the protein expressions of ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor B1 and the change of extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway. Results Liraglutide could significantly reduce the fluorescence density of HepG2 cells in high glucose (50 mmol/L) condition, increase the expression of ABCA1 protein and enhance the phosphorylation level of ERK1/2.Conclusion Liraglutide can promote cholesterol efflux in HepG2 cells under high glucose condition, and its mechanism may be related to the regulation of ERK1/2 signaling pathway and the up-regulation of ABCA1 expression.