Abstract: To explore the effect of glucagon-like peptide-1 receptor agonist-Exendin-4 (Ex-4)on murine MIN6 pancreatic β-cells apoptosis induced by oxidative stress，the morphological changes of cell damage were evaluated by epifluorescence microscopy after staining with AO-EB. The percentage of cell apoptosis was determined by flow cytometric assay after Annexin-V-FITC-PI staining. Nitric oxide level was measured by Griess reagent assay. Inducible nitric oxide synthase (iNOS) protein and NF-κBp65 fragment were detected by Western blotting. Ex-4 inhibited the increase of nitrite level and percentage of apoptosis induced by t-BHP in MIN6 cells. Furthermore, Ex-4 partly reduced the expression of iNOS protein and the ratio of NF-κBp65 protein in nucleus:cytosol induced by t-BHP. These results suggest that Ex-4 protects MIN6 pancreatic β-cells from oxidative stress-induced apoptosis via down-regulation of NF-κB-iNOS-nitric oxide pathway.