ObjectiveEffect of fluoride on proliferation and differentiation of osteoblast in rats was studied. MethodOsteoblasts were obtained from the calvaria of 24h new born Wister rat with enzymic digestion method and cultured in the medium containing 10 -7 mol/L to 10 -3 mol/L NaF. The cell proliferation was determined with MTT method. The activity of alkaline phosphatase(ALP) was measured with PNPP method. Osterocalcin was examined with the radioimmunologic assay(RIA). ResultNaF increased the proliferation of rat osteoblast at low doses(10 -7 mol/L~10 -5 mol/L), while at high does(10 -4 mol/L,10 -3 mol/L) it decreased the proliferation. Effects of NaF on differentiation of osteoblast were varied. The influence of NaF on ALP activity was similar to that of cell proliferation. However, all concentrations of NaF used stimulated the secretion of osterocalcin. ConclusionFluoride had two-phase effection proliferation and early differentiation of osteoblast. At low doses it promoted while at high doses it had a negative effects. But the action of late differentiation was single.