Background There are no conclusive studies evaluating the interaction between icariin and exercise for treatment of osteoporosis; the efficacy and safety of this treatment combination remains to be evaluated.The purpose of this study was to investigate the effects of icariin treatment combined with exercise therapy on bone parameters and body weight of ovariectomized rats.Methods Ovariectomized rats were used as a model of postmenopausal osteoporosis and were exposed to either icariin treatment,exercise,hormone replacement therapy,or a combination of the above.Untreated,ovariectomized rats and sham operated rats were used as controls.After 3 months of experimental interventions the effects of the treatments on the body and uterine weights,the physical and biomechanical properties of bones,and the expression of the osteoblast-specific gene Osterix (Osx),were assessed.Results The weight gain of the ovariectomized rats was greater than that of the treated experimental groups.Uterine weight and serum estradiol levels were significantly greater in sham operated and estrogen-treated ovariectomized rats than in the other groups.Biomechanical parameters were improved significantly in ovariectomized rats treated with exercise alone or treated with exercise and icariin.Osx expression was increased in ovariectomized rats treated with exercise and icariin or treated with just icariin.Conclusions Exercise combined with icariin had a synergistic effect in the early prevention of osteoporosis in ovariectomized rats.The effects of icariin and exercise on osteoporosis are worth further exploration.