Thirty-one 3-month-old Female Sprague-Dawley rats were randomly divided into 5 groups, basal control (group 1, killed at the begining), aging control (group 2), ovariectomized (OVX, group 3), OVX with nilestriol treatment group (group 4) and OVX with osthole treatment group (group 5). Group 2 and group 3 ig with water 5 ml.kg-1 and group 5 ig with osthole 6.7 mg.kg-1, all once a day for 6 d; group 4 ig with nilestriol 1 mg.kg-1, once a week. After 12 weeks, all rats were killed. The proximal tibiae of rats were processed to undecalcified sections at 20 microns thickness for histomorphometric analysis. OVX was shown to reduce markedly the trabecular bone mass (%Tb. Ar-59%) due to increase of bone turnover with the result that bone resorption exceeded bone formation, as compared with aging controls. In contrast, treatment of OVX rats with Osthole and nilestriol increased significantly the trabecular area (increased 68% and 27.1% compared with that of OVX respectively). Our results indicate that osthole and nilestriol treatment provides protection against osteoporosis in OVX rats. The protective mechanism of osthole and nilestriol involves supression of bone turnover, but the effects of osthole is lower than that of nilestriol (trabecular area decreased 55% more in osthole group than that with nilestriol treatment). Our finding may provide theoretical evidence for the clinical use of osthole or nilestriol for treatment and prevention of osteoporosis.