Abstract: Objective To study the effect of raloxifene and estradiol on the biological function and osteoprotegerin expression of osteoblasts in vitro. Methods Different doses of raloxifene and estradiol were added into the medium of the second generation osteoblasts from the shull of newborn SD rats.The proliferation,differentiation,mineralization and osteoprotegerin expression of the osteoblasts in different groups were observed. Results Raloxifene had no significant effects on stimulating the proliferation,the expression of osteoprotegerin and the formation of mineral nodes of the cultured osteoblasts (the trial vs the control,P>0.05).However,raloxifene can significantly improve the alkaline phosphatase activity of the cultured osteoblasts (the trial vs the control,P<0.05).Estradiol significantly increased the proliferation of osteoblasts,and differentiation,minera- lization,expression of osteoprotegerin(P<0.01 vs the control). Conclusion The effects of raloxifene and estradiol on the cultured osteoblasts are different,which implied their different mechanisms in inducing osteoporosis.