In order to examine the involvement of leptin in the ossification of spinal Ligaments (OSL), the present study examined (i) serum levels of leptin and insulin in OSL patients and controls, (ii) serum leptin levels in children of OSL females with severe obesity (iii) the expression of leptin receptor mRNA in human spinal ligaments, and (iv) effects of leptin on cultured human ligament cells. In the OSL females, serum leptin levels were significantly higher than those of the control females, and the levels were positively correlated to the serum insulin levels, while in the control females, there was a tendency of inverse correlation, The daughters of OSL females with severe obesity also had high serum leptin levels, although they had not developed OSL, The expression of leptin receptor mRNA was confirmed in the ligaments, but leptin did not influence the alkaline phosphatase activity nor procollagen type I carboxyl-terminal peptide content of the ligament cells. These findings suggest that leptin is involved genetically and indirectly with the pathogenesis of OSL in female patients.