Aim To investigate the mechanism of Sortilin in diabetic vascular calcification. Methods Thirty patients with diabetic foot amputation were enrolled from June 2015 to June 2017. The calcification of anterior tibial artery was measured by calcium quantification and divided into control group (calcium concentration＜2 μmol/mg, n＝15) and calcification group (calcium volume≥2 μmol/mg, n＝15). Western blot was used to determine the expression of Sortilin in the two groups. And the serological and clinical indexes were also analyzed. The model of diabetic vascular calcification was established based on human aortic smooth muscle cell line (HA-VSMC). The degree of calcification was detected by alizarin red staining. The expression level of Sortilin in the model was detected by Western blot. The calcification model was then treated with Sortilin and Sortilin antibody, and the effect of Sortilin on the calcification model was shown by von Kossa staining, calcium quantification and calcium nodule diameter measurement. Results Calcification of the anterior tibial artery in the calcification group was 4.9 times that of the control group, and the expression level of Sortilin increased by 3.92 times. After treatment with calcified culture medium containing Nε-carboxymethyl-lysine (CML) and oxidized low density lipoprotein (ox-LDL), HA-VSMC calcification increased significantly. The calcification of HA-VSMC was obviously increased under the stimulation of Sortilin recombinant protein, and the diameter of calcium nodules was also significantly increased. Meanwhile, tissue non-specific alkaline phosphatase (TNAP) expression levels were also significantly increased. Conclusion Sortilin promotes the formation of diabetic vascular calcification and develops it into macrocalcification.