Methionine is a specific amino acid which contains sulfur, and can be used to make proteins, found in fish, meat, and dairy products, the excess intake of L-methionine lead to elevated homocysteine (Hcy) level that known as Hyperhomocysteinemia (HHcy). Increased Hcy plasma may represent an independent risk factor for osteoporotic fractures, and therefore may also negatively affect bone metabolism. This study was designed to examine the impact of Hcy on osteoclast activity in Male Rabbits, following methionine overload. To achieve this study's aims, we recruiting (20) males of New Zealand white rabbits that were divided into (10/group) control group and a group treated with methionine. Then after the intubation of methionine overload, we measured the "Receptor Activator of Nuclear factor Kappa-b" (RANK) and "Receptor Activator of Nuclear factor Kappa-b ligand" (RANK-L) levels in the blood, in addition to histological examination of the trabecular structure of femur bone. The results show a significant (p≤0.001) increase in serum RANK and RANK-L levels of methionine treated group in comparison with the control group. The histological examination of the trabecular structure of femur bone shows an increase in osteoclasts percentage, activity, and large resorption pits in the methionine treated group. The HHcy that was induced by methionine overload, caused an increase in osteoclast activity and numbers in male rabbits suggested a mechanistic role for bone resorption by Hcy. Future research clarifying the mechanistic function of elevated concentrations of Hcy in osteoporosis may have important therapeutic implications.