A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test, alkaline phosphatase ( ALP) activity measurement, mineralized function, Oil Red O stain and measurement were employed to assess the effect of Dy3+ on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells (BMSCs) and the adipogenic trans-differentiation of mouse primary osteoblasts (OBs). The results showed that Dy3+ had no effect on BMSC proliferation at concentrations of 1 x 10(-8) and 1 x 10(-5) mol/L, but inhibited BMSC proliferation at other concentrations. Dy3+ had no effect on OB proliferation at concentrations of 1 x 10(-10) and 1 x 10(-9) mol/L, but inhibited OB proliferation at other concentrations. Dy3+ had no effect on the osteogenic differentiation of BMSCs at concentrations of 1 x 10(-9) and 1 x 10(-7) mol/ L, and promoted osteogenic differentiation of BMSCs at other concentrations at the 7th day. The osteogenic differentiation of BMSCs was inhibited by Dy3+ at concentration of 1 x 10(-5) mol/ L at the 14th day, but promoted osteogenic differentiation of BMSCs at concentrations of 1 x 10(-9), 1 x 10(-8), 1 x 10(-7) and 1 x 10(-6) mol/ L with the maximal effect at concentration of 10(-6) mol/ L. Dy3+ promoted mineralized function of BMSCs at any concentration. Dy3+ had no effect on adipogenic differentiation of BMSCs at concentration of 1 x 10(-7) mol/ L, but inhibited adipogenic differentiation of BMSCs at other concentrations. Dy3+ inhibited adipocytic trans-differentiation of OBs at any concentration, suggesting that Dy3+ had protective effect on bone and the protective effect on bone may be mediated by modulating differentiation of BMSCs away from the adipocyte and inhibiting adipocytic trans-differentiation of OBs which may promote differentiation and mineralization of OBs. These results may be valuable for better understanding the mechanism of the effect of Dy3+ on pathogenesis of osteoporosis.