Aim: The present study aimed to determine the effect of Estradiol, Imipramine and Fluoxetine on brain serotonin levels in ovariectomized-induced osteoporotic rats and to investigate the effect of previous treatments on Electron Microscope results in rats. Methods: Rats were subjected to bilateral ovariectomy. After 2 weeks from operations, rats were treated with Estradiol, Imipramine and Fluoxetine for 14 days. At the end of 6 weeks animals were sacrificed and serotonin levels of brain tissue were determined. Electron microscope examination of femoral bone was also performed. Results: Treatment with Estradiol, Imipramine and Fluoxetine could treat depressive symptoms caused by ovariectomy which was observed in brain serotonin levels. Treatments could decrease the levels of brain serotonin by 28.73%, 35.25% and 32.14% respectively. Regarding Electron microscope, imipramine could partially improve bone structure while estradiol and fluoxetine could significantly restore bone mass compared to the corresponding osteoporosis group. Conclusion: In conclusion, Estradiol, imipramine and fluoxetine could treat depressive symptoms caused by ovariectomy in rats. Treatments have also shown restorative effects on bone structure in ovariectomized-induced osteoporotic rats.