Aim To study the regulatory effect and molecular mechanism of glucagon-like peptide-1 (GLP-1) on pyroptosis of umbilical vein endothelial cells (HUVEC) induced by oxidized low density lipoprotein (ox-LDL). Methods HUVEC was cultured and divided into control group, ox-LDL group, GLP-1 group (10 nmol/L, 100 nmol/L, 1 000 nmol/L), GLP-1+miR-22 inhibitor group, miR-22 inhibitor group, miR-22 mimic group, negative control (NC) inhibitor group and NC mimic group. Flow cytometry was used to detect apoptotic rate, fluorescence quantitative PCR was used to detect the expression of microRNA-22(miR-22), Western blot was used to detect the expression of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1, enzyme-linked immunosorbent assay was used to detect the content of interleukin 1beta (IL-1β) and interleukin-18(IL-18). Results Compared with the control group, the apoptotic rate, the expression of NLRP3, ASC, caspase-1 in cells and the levels of IL-1β and IL-18 in the culture medium of ox-LDL group significantly increased, while the expression of miR-22 significantly decreased (P<0.05). Compared with ox-LDL group, the apoptotic rate, the expression of NLRP3, ASC, caspase-1 in cells and the levels of IL-1β and IL-18 in the culture medium of GLP-1 group significantly decreased, while the expression of miR-22 significantly increased (P<0.05). Compared with GLP-1 group, the apoptotic rate, the expression of NLRP3, ASC, caspase-1 in cells and the levels of IL-1β and IL-18 in the culture medium of GLP-1+miR-22 inhibitor group significantly increased, while the expression of miR-22 significantly decreased (P<0.05). The expression of NLRP3, ASC, caspase-1 in cells and the levels of IL-1β and IL-18 in the culture medium of miR-22 inhibitor group were significantly higher than those of NC inhibitor group, while the expression of NLRP3, ASC, caspase-1 in cells and the levels of IL-1β and IL-18 in the culture medium of miR-22 mimic group were significantly higher than those of NC mimic group. Conclusion GLP-1 can alleviate ox-LDL-induced endothelial cell pyroptosis through the miR-22/NLRP3 pathway.