Aim To explore the role of activated T-cell cytoplasmic 1 (NFATc1) in diabetic vascular calcification. Methods Fifteen patients with diabetic foot amputation were enrolled. Serum and anterior tibial arteries were collected. According to the calcium content of the anterior tibial arteries, patients were divided into low-calcification group and high-calcification group. The NFATc1 levels in serum and anterior tibial arteries were detected, and their correlation with the calcium content of anterior tibial arteries was analyzed respectively. An in vitro model of diabetic vascular calcification was constructed with mouse aortic smooth muscle cell (MASMC)to detect the phenotypic transition and calcium deposition of MASMC under high glucose. Furthermore, siRNA was used to silence NFATc1 to determine the effect of NFATc1 on MASMC phenotype transition and calcium deposition. Results The NFATc1 level of the high-calcification group was significantly higher than that in the low-calcification group both in serum and in anterior tibial arteries. And correlation analysis showed that the serum and anterior tibial artery NFATc1 levels were positively correlated with calcium content. In the in vitro model of MASMC, high glucose significantly weakened the contraction phenotype of MASMC, promoted the osteogenic phenotype transdifferentiation, and significantly increased the calcium deposition. The effect of high glucose in promoting phenotypic transition and promoting calcification was not connected with its hypertonicity. After silencing NFATc1 with siRNA, the osteogenic differentiation of MASMC was significantly inhibited, and calcium deposition was also significantly reduced. Conclusion NFATc1 can promote the transdifferentiation of vascular smooth muscle cell to an osteogenic phenotype and promote the progression of diabetic vascular calcification.