The aim of the present study is to test the hypothesis that extraskeletal calcifications regress in uremic rats after reduction in phosphorus intake and treatment with calcimimetics. Extraosseous calcifications were induced in five-six nephrectomized rats fed a high phosphorus (P) (1.2%) diet receiving calcitriol, 80 ng/kg ip every other day for a period of 14 days. Next, dietary P was reduced to 0.6% and rats were treated with vehicle (n=20), calcitriol, 80 ng/kg ip/48h (n=20), or the calcimimetic AMG 641, 1.5 mg/kg sc/48 h (n=20). Aortic and soft-tissue calcium and phosphorus content was evaluated after 14 and 28 days. At 28 days, reduction of phosphorus intake resulted in significant decrease in tissue mineral content in vehicle- and AMG 641-treated rats but not in rats receiving calcitriol. Aortic CaxP was lower in rats treated with AMG 641 (96.7±26.4 mg/g) than in rats receiving vehicle (178.3±38.6 mg/g). An infiltrate of phagocytic cells expressing the calcium-sensing receptor was identified in areas surrounding foci of calcification. Additional studies in parathyroidectomized rats demonstrated that AMG 641 increased the urinary excretion of calcium (6.2 ± 0.6 vs 3.1 ± 0.5 mg/day (vehicle), P<0.001). In conclusion, experimentally-induced extraosseous calcifications in uremic rats can be partially resolved by reducing phosphorus intake; the addition of calcimimetics may accelerate the regression process through mechanisms potentially involving a direct stimulatory effect on mineral-phagocytic cells plus an increase in urinary calcium excretion.