Aim To investigate the role of Ghrelin in diabetic vascular calcification. Methods Thirty cases of diabetic foot amputation patients from the Affiliated Hospital of Jiangsu University were enrolled. The tibial artery stenosis of patients were divided into three groups according to Doppler ultrasound:mild stenosis group (stenosis＜50%)(n=10), moderate stenosis (50%≤stenosis＜70%)(n=10) and severe stenosis / occlusion group (70%≤stenosis≤ 100%)(n=10). Serum and clinical related indicators detection, HE staining, Von Kossa calcium staining, vascular calcium content, alkaline phosphatase(ALP)activity assay and Western blot assay were performed. Results Consistent with ultrasound results of diabetic amputee tibial artery, HE staining and Von Kossa staining showed:there were a lot of diffuse black membrane calcium in the tibial arteries of three groups; but compared with mild stenosis group and moderate stenosis group, there were a lot of spotty black calcium deposition (hard hyperechoic plaque in ultrasound) in the tibial artery atherosclerotic plaques of severe stenosis / occlusion group. Quantitative tests showed the ALP activity and calcium content of tibial artery increased significantly in severe stenosis group, they were 2.44 times and 2.39 times for mild stenosis group respectively, but compared with mild stenosis group,there was no statistically significant difference in the moderate stenosis group. Western blot assay showed the expression of osteoprotegerin(OPG) were reduced, while the expression of receptor activator of nuclear factor kappa B ligand(RANKL) was up-regulated. According to Pearson correlation analysis we observed a negative correlation between tibial artery calcium content and Ghrelin (r=－0.64, P<0.001) as well as between Ghrelin and sRANKL (r=－0.85, P<0.001),while OPG was positively correlated with Ghrelin (r=0.85,P<0.001). Conclusion With the extent of vascular calcification in diabetic patients worsing, the expression of Ghrelin and OPG were down-regulated, while the expression of RANKL was up-regulated, suggesting serum Ghrelin, OPG/sRANKL levels may have an early-warning value.