Abstract: Objective To investigate the potential beneficial effects of endothelin receptor antagonist bosentan on vascular disease in diabetic mice and its mechanism. Methods Sixty 6-week-old male C57BL/6 mice were divided into 3 groups:control group, diabetes group and diabetes with drug intervention group.Streptozotocin(STZ) was intraperitoneally injected at a single dose of 70 mg/kg to establish diabetes model.The fasting blood glucose from tail vein sample was tested to verify diabetes model.Bosentan(100 mg/kg) was given by intragastric administration once a day after STZ injection for 8 weeks in diabetes with drug intervention group, and the same amount of 0.9% sodium chloride injection was given to control group and diabetes group.After 8 weeks, aortic HE staining results in each group and mRNA expression of vascular endothelial growth factor(VEGF), endothelin-1(ET-1), tumor necrosis factorα(TNF-α), matrix metalloproteinases 2(MMP-2), matrix metalloproteinases 9(MMP-9) were observed by qRTPCR. Results HE staining results showed that aortic intima was generally normal in control group, while there were atherosclerotic plaque formation and a large number of inflammatory cell in diabetes group and the plaque burden lightened obviously in diabetes with drug intervention group.qRT-PCR results showed that the mRNA level of VEGF in diabetes group and diabetes with drug intervention group were significantly lower than those in control group(P< 0.05), while the mRNA expression of ET-1, TNF-a, MMP-2, MMP-9 in diabetic group and diabetes with drug intervention group increased significantly when compared with control group(P< 0.05).The mRNA expression of VEGF in diabetes with drug intervention group was higher than that in diabetes group(P< 0.05) and the mRNA expressions of ET-1, TNF-a, MMP-2 and MMP-9 in diabetes with drug intervention group were lower than those in diabetic group(P< 0.05). Conclusion Endothelin receptor antagonist bosentan has beneficial effects on vascular complications in diabetic mice.