Objective To investigate the protective effect and mechanism of pamidronate disodium on calcification in rat vascular smooth muscle cells (RVSMCs) induced by hyperphosphate.Methods RVSMCs were placed in various culture mediam, including normal phosphate medium (Pi 1.4 mmol/L), high phosphate medium (Pi 4.5 mmol/L), different pamidronate disodium concentrations medium (Pi 4.5 mmol/L+pamidronate disodium 10-5, 10-6, 10-7 mmol/L). Calcium content and cell protein content were quantified by the O-cresolphthalein complexone method and BCA protein assay respectively. Calcification was visualized by yon Kossa staining, and cbfα-1,osteocalcin were quantified by Western blotting. Results After culture for 3 days, calcium content in high phosphate group were much higher than that in control group, and pamidronate disodium groups had a lower calcium content compared with high phosphate group (all P＜0.05).Calcium deposit in RVSMCs was greater in high phosphate group, while pamidronate disodium groups revealed obviously decreased deposit (all P＜0.05). Protein expression of cbfα-1 and osteocalcin in pamidronate disodium groups was much lower than that in high phosphate group.Conclusion Pamidronate disodium can protect RVSMCs from phosphate-induced calcification in vitro, which may be associated with the blockage of transformation of RVSMCs into osteoblast.