Background: Excess thyroid hormone activates osteoblast and osteoclast functions leading to high bone turnover and bone loss. L Carnitine (LC) is considered a peripheral antagonist to thyroid hormone action. It inhibits thyroid hormone entrance into the tissue nuclei. Aim: To evaluate the protective role of LC on the biochemical, histological and immunohistochemical effects of hyperthyroid-induced osteoporosis in adult male albino rats. Materials and Methods: A group of 32 adult male albino rats whose weights ranged between 180 and 230 gm was distributed into four groups; control group: The animals had only regular diet and tap water, T4 treated group: received L thyroxine (T4) powder dissolved in a dose of 2 μg/ml/day for 30 days by gavage, T4+LC treated group: a combination of T4 powder dissolved in drinking water at a dose of 2 μg/ml/ day for 30 days by gavage and LC (500 mg/kg) intraperitoneal injection, and LC treated group: received LC in a dose of (500 mg/kg) for 30 days by intraperitoneal injection. Femur specimens were demineralized using EDTA solution then stained for histological and immunohistochemical study. Histomorphometry and statistical analysis were done to estimate the cortical thickness of femur diaphysis and the area percentage of collagen fibers in the previously mentioned groups. Results: Induced hyperthyroidism caused serological, histopathological, immunohistochemical, and morphometric alterations in the cortical diaphysis of adult male albino rat femur. There was an increase in the serum level of T3, T4, ALP in the T4 treated group causing osteoporotic changes and a decrease in the cortical thickness of femoral diaphysis. Also, strong OPN and iNOS immunoreactivity in the cytoplasm of osteocytes and osteoporotic cavities was observed. Co-administration of LC protected against such changes. Conclusion: The study highlights the improvement of the histological and immunohistochemical changes of rats femur caused by L thyroxine after co-administration of LC.