Objective: To observe the effects of the soybean isoflavaones on the mRNA expression of osteoprotegerin(OPG),osteoclast differentiation factor(ODF) and macrophage colony stimulating factor(M-CSF) in bone tissue of ovariectomized rat, and to investigate the possible pathway to prevent and treat postmenopausal osteoporosis using soybean isoflavaones. Methods: Thirty healthy adult SD rats were randomly divided into 3 groups: sham-operated group, ovariectomized group and soybean isoflavaones treated group. All rats were ovariectomized except those in sham-operated group. The bone density of the 3-6th lumbar vertebrae was detected after 12 weeks.Total RNA was extracted from femur bone and the mRNA expression of OPG, ODF and M-CSF was examined by real time PCR.Results: Soybean isoflavaones increased the bone density of the lumbar vertebrae in ovariectomized rat and up-regulated the expression of OPG, whereas down-regulated the expression of M-CSF and the ratio of ODF to OPG. Conclusion: The effects of soybean isoflavaones on postmenopausal osteoporosis are tightly correlated with OPG, M-CSF and the ratio of ODF to OPG.