This study was conducted in order to evaluate the effect of sericin-calcium (SC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after ovariectomy (OVX), Sprague-Dawley rats were divided randomly into three groups: sham-operated group (Sham), ovariectomized group, and SC-treatment group (OVX+SC). Rats in the OVX+SC group were given drinking water containing 0.07% SC for eight weeks. Bone breaking force, mineralization, and blood parameters related to bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol showed a significant decrease, while osteocalcin and type I collagen C-terminal telopeptides (CTx) showed an increase. Breaking force of femurs as well as bone mineral density (BMD), ash, calcium, and phosphorus in femurs showed a significant decrease following OVX. Treatment with SC (0.07% in drinking water) resulted not only in remarkable restoration of the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also led to recovery of decreased femoral breaking force, BMD, ash, calcium, and phosphorus. It is suggested that SC effectively improves bone density by preventing bone turnover-mediated osteocalcin, CTx, and minerals, and that it could be a potential candidate for use in therapy or prevention of post-menopausal osteoporosis.