The results of previous studies on the relationship between leptin and blood pressure are discordant. We investigated to what extent the serum leptin level was related to blood pressure independent of the degree of insulin resistance. The subjects were 1916 men aged 34-69 years whose mean body mass index (BMI) was 23.0 kg/m2. Blood pressure was regressed by leptin concentrations with adjustments for age, BMI, insulin resistance, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, physical activity, drinking habits and smoking status. Leptin was associated with diastolic blood pressure (DBP) (standardized beta: 0.092, p = 0.003), but not with systolic blood pressure (SBP) (standardized beta: 0.035, p = 0.25), although insulin resistance was positively associated with both SBP and DBP (standardized beta: 0.175 for SBP, p < 0.001 and 0.114 for DBP, p < 0.001) among all subjects. After subjects were divided into those with normal blood pressure (SBP <130 mmHg and DBP <85 mmHg) and those with higher blood pressure, leptin was positively and significantly associated with DBP (standardized beta: 0.106, p = 0.012) independent of the degree of insulin resistance, but not with SBP (standardized beta: 0.064, p = 0.13) among subjects in the normal blood pressure range. Among the subjects with higher blood pressure, however, neither the association of leptin with SBP nor that of leptin with DBP was statistically significant. These findings suggest that leptin may maintain and increase arterial tone, resulting in the elevation of DBP only within normal blood pressure range. It is also likely that leptin is a physiological mediator--or at least a marker--of some degree of DBP elevation in obesity.