OBJECTIVE: To investigate the protective effect of clomiphene citrate on bone resorption in the tibial bones of ovariectomized rats via biochemical and immunohistochemical methods. STUDY DESIGN: A total of 32 Wistar rats were randomly and equally divided into 4 groups: (I) sham, (II) clomiphene citrate, (III) bilateral ovariectomy, and (IV) bilateral ovariectomy+clomiphene citrate. Following ovariectomy the animals in Group IV were given intraperitoneal 10 mg/kg clomiphene citrate daily for 2 months. After 2 months the animals were sacrificed under anesthesia. Blood samples were taken from each animal, and the values of estrogen, calcium, and alkaline phosphate were examined. There were significant differences in the biochemical and immunohistochemical expression values between the sham group (1) and the group with ovariectomy (3), as well as between the ovariectomy groups±clomiphene citrate (p<0.001). RESULTS: The ovariectomy+clomiphene citrate group had a reduction in the number of osteoclast cells in which the bone trabecular areas were resorbed. We observed that osteoblasts formed new bone formation with bone matrix around bone trabeculae in the clomiphene citrate–treated group after ovariectomy. CONCLUSION: Our data suggest that clomiphene citrate increased osteoblastic activity against bone loss, which is an important consequence of estrogen deficiency in bone resorption due to ovariectomy. This increase in osteoblastic activity induced osteocyte development and stimulated the regeneration of bone and bone matrix formation. © Science Printers and Publishers, Inc.