AimTo explore the effect and mechanism of pioglitazone on vascular calcification (VC) in diabetic rats.MethodsRat model of vascular calcification and diabetes (DM) was established by injection of vitamin D3 plus warfarin and streptozocin(STZ).Thirty six ten-week-old male SD rats were randomely divided into six groups: control group, DM group, VC group, VC+DM group, VC+PIO group, VC+DM+PIO group.Calcification was confirmed by Von Kossa staining, and calcium content and alkaline phosphatase (ALP) activity of the vascular tissue were measured.The expression of osteoprotegerin (OPG) mRNA and protein were examined by qRT-PCR and immunohistochemistry.ResultsMassive black granules were observed in the vascular smooth muscle cells and interstitial tissue by Von Kossa staining in VC group and VC+DM group.Calcium content and ALP activity of VC+DM group were 3.63 times and 1.35 times higher than DM group, and 3.69 times and 1.30 times（p<0.05）higher than VC group, but the expression of OPG mRNA and protein were reduced（p<0.05）.Calcium content and ALP activity of VC+DM+PIO group decreased 13.70% and 18.04% than VC+DM group（p<0.05）, but the expression of OPG mRNA and protein increased（p<0.05）.ConclusionPioglitazone can reduce the degree of vascular calcification and increase the expression of OPG mRNA and protein.OPG is likely to be one of the main factors of inhibiting vascular calcification.