Objective      To observe the effect of Exendin-4（Ex-4）on nitric oxide (NO）release from pig iliac endothelial cells (PIEC) and its relation with intra- and extracellular calcium concentrations.       Methods      Glucagon-like peptide-1 receptor (GLP-1R) was detected in PIEC with immunofluorescence assay. Effect of Ex-4 on NO release from PIEC was detected by Griess diazonium reaction in medium with calcium or without calcium. Intracellular calcium concentration was measured with a flow cytometer. Relation between time and concentration effectiveness of Ex-4-induced NO release from PIEC was assessed. Effect of Ex-4 on NO release from PIEC was observed after pretreated with the eNOS signal blocker

L-NAME.       Results      The GLP-1R was expressed in PIEC. Ex-4 stimulated the NO release from PIEC in a dose- and time-dependent manner. The intracellular calcium concentration was higher than the extracellular calcium concentration (62.67±1.53 vs 57.36±1.42，P0.01）. The NO release level was significantly higher from PIEC in the medium without calcium than in the medium with calcium (2.014±1.040 vs 1.624±0.424 μmol/L

P=0.03）. The Ex-4-induced NO release from PIEC after pretreatment than before pretreatment with L-NAME（P0.01）.       Conclusion      Ex-4 increases NO release from PIEC by activating eNOS. The role of Ex-4 in activating eNOS may be related with the intracellular calcium concentration.