Aim To study the effects of hypercalcinemia on vascular calcification of rat. Methods Arterial calcification of Sprague-Dawley rats was induced by vitamin D3 plus nicotine (VDN). Calcification was confirmed by von Kossa staining, measurerment of calcium content, 45 Ca2+ accumulation and alkaline phosphatase (ALP) activity of intracellular and vascular tissue. Semi-quantitative-reverse transcription polymerase chain reaction(RT-PCR) was used to determine osteopontin(OPN, a marker of calcification) and β-actin mRNA level. Results The results showed that VDN treated rat showed a higher systolic pressure by 28% (P<0.05) than that in control rat. Von Kossa staining for calcification, showed strong positive staining as black/brown areas among the elastic fibers of the medial layer in calcified aorta. The aortic calcium content, 45 Ca2+ accumulation and ALP activity in calcified arteries were increased by 3.7-fold, 1.3-fold and 1.4-fold respectively (P<0. 01), compared with control. The amount of OPN mRNA in calcified aorta was elevated by 46% (P<0.01) compared with that of control. High dose calcium uptake increased plasma calcium content and decreased phosphate level (2.49±0.14 vs 2.20±0.12 and 1.25±0.05; 1.40±0.07, P<0.01) compared with control. There are no significant changes in aortic calcium content, 45 Ca2+ accumulation and ALP activity in high dose calcium treatment alone. However, high dose calcium can aggravate vascular calcification of rat treated with VDN. The aortic calcium content, 45 Ca2+ accumulation, ALP activity and OPN mRNA level were increased by 12% (P>0.05), 38%(P<0.01), 15%(P<0.01), and 34%(P<0.01), respectively, in rat treated with VDN and high dose calcium, compared with that in rat treated with VDN alone. Conclusions High dose calcium uptake can aggravate vascular calcification of rat.