Aim We employed rat vascular calcific model induced by vitamin D 3 intramuscular injection and oral nicotine, and rat calcific vascular smooth muscular cells (VSMC) induced by β-glycerophosphate to study the possible mechanism which was involved in the regulatory action of ghrelin in vascular calcification. Methods The total aorta Ca content in aorta and VSMC were measured by atom absorptive spectrophotography; the alkaline phosphatase (ALP) activity were determined by the use of phenyl diphosphate-2-sodium; aortic 45 Ca-deposition was detected with the using of 45 CaCl 2; the mRNA expression of ghrelin, osteopontin (OPN) and endothelin were analyzed by reverse-transcript PCR, and the levels of ghrelin in plasma, endothelin in plasma and aorta were determined by radioimmunoassay. Results Vitamin D 3 and nicotine induced vascular calcification in rats and β-glycerophosphate induced calcification in VSMC too. The calcification in aorta was significantly attenuated by subcutaneous administration with ghrelin 30 and 300 nmol/kg for 4 weeks, and the latter dosage was more potent than the former. After the ghrelin treatment, the total aorta Ca 2+ contents, aortic 45 Ca-deposition, ALP activity were less respectively, than those in the rats with vascular calcification, but the OPN mRNA was up-expressed. After treated with ghrelin 10 -8～10 -6 mol/L, the calcification in VSMC was also attenuated, with decrease in the total Ca 2+ content, 45 Ca-deposition and ALP activity in VSMC in a concentration-dependent manner, so did the increase in OPN mRNA expression. In addition, we observed that endothelin levels of plasma and aorta and aortic endothelin mRNA expression significantly increased in the rats with vascular calcification, and ghrelin treatment significantly decreased them, with high dosage more portent than the lower. Conclusion Our results indicated that ghrelin can significantly attenuate the calcification in aorta and VSMC partly through the antagonism with endothelin system in circulation and vascular tissues.