【Abstract】Objective To study the effect of hyperphosphate on calcification and osteoprotegerin (OPG) mRNA expression in rat vascular smooth muscle cells (RVSMCs), and the protection effect of OPG on RVSMCs calcification induced by hyperphosphate. Methods RVSMCs were cultured in normal phosphate medium, high phosphate medium, caspase inhibitor Z-VAD-FMK containing medium or OPG containing medium. Calcium content was quantified by the o-cresolphthalein complexone method, and protein content by the BCA method. RVSMCs calcification was visualized by Von Kossa staining. OPG mRNA was measured by semi-quantitative RT-PCR, and cell apoptosis was assayed by flow cytometry. Result (a) At the culture for 3, 6 and 9 days, RVSMCs calcification occurred more frequently in cells cultured in high phosphate medium than those in normal phosphate medium (P＜0.05); (b) At the culture for 6 days, calcium deposition in RVSMCs was significantly inhibited in the cells cultured in 1.0μM/L and 2.0μM/L Z-VAD-FMK containing media (P＜0.05), and in those cultured in 10μg/L and 100μg/L OPG containing media (P＜0.05); (c) OPG mRNA increased in cells cultured in high phosphate medium, compared to those in normal phosphate medium; (d) Apoptosis and calcification of RVSMCs occurred fрĀ_Ā꿾㣰豀꘾y in those cultured in high phosphate medium. OPG significantly inhibited apoptosis in RVSMCs. Conclusion Hyperphosphate induces calcification of RVSMCs possibly through the induction of cell apoptosis. OPG protects RVSMCs from phosphate-induced calcification through inhibiting cell apoptosis.