Aim To investigate the effect of glucagon-like peptide-1 receptor agonist Exenatide on vascular endothelial dysfunction in diabetes mellitus rats.Methods 34 Healthy male Wistar rats were randomly divided into 4 groups: control group,diabetes model group,low dose of Exenatide treatment group(0.3125 μg/day),and high dose of Exenatide treatment group(0.625 μg/day).The last three groups were experienced oral glucose tolerance test and fasting insulin level detection after administrated with high fat emulsion for 14 days.After that diabetes mellitus models were established by streptozotocin injected intraperitoneally,with fasting glucose level≥11.8 mmol/L as a model successful marker.After treatment with Exenatide(injected hypodermically) for 45 days,fasting glucose levels were detected.Thoracic aortas were isolated to detect the responses to norepinephrine,acetylcholine and sodium nitroprusside.The expression of von Willebrand factor was detected by immunohistochemistry.Results After high fat emulsion administration for 14 days,the results of oral glucose tolerance test were abnormal,the glucose levels at every time-point were elevated significantly compared with control group rats(P<0.01).Besides that,both fasting insulin levels [(49.2±13.0)×10-3 μU/L] and homeostasis model assessment of insulin resistance index(11.7±3.5)were higher than control group[(35.7±4.7)×10-3 μU/L,7.7±1.1,both P<0.05],all these implied that insulin resistance arose.Compared with control group(4.6±0.4 mmol/L),the fasting glucose levels of diabetes model group(23.3±1.9 mmol/L)were increased significantly,both low dose(20.9±1.4 mmol/L)and high dose(20.2±1.4 mmol/L)of Exenatide treatment could attenuate the elevated fasting glucose levels(P<0.05,P<0.01 respectively).The responses to acetylcholine(P<0.01,P<0.05)and low-dose(10-8 mol/L and 10-7 mol/L) sodium nitroprusside(P<0.05)and the expression of von Willebrand factor were decreased significantly in diabetes model group.Except of response to sodium nitroprusside,two other parameters were improved obviously after treatment with either low dose or high dose of Exenatide(both P<0.05).There was no significant difference in response to norepinephrine among groups.Conclusion Exenatide treatment could reduce blood glucose level and attenuate the vascular endothelial dysfunction in diabetes mellitus rats.