Insulin resistance is thought to raise blood pressure. Recently, a significant positive relationship between mean blood pressure and plasma leptin levels, but there have been no reports dealing with the relationship between blood pressure and either insulin resistance or serum leptin levels after weight loss. In the present work, we attempted to clarify the relationship between changes in blood pressure and either the serum leptin level or the insulin level in 102 moderately obese females (mean body mass index (BMI), 29.5±0.5 kg/m²; age, 47.0±0.9) during a 3 month period. No differences in age, fat-mass, homeostasis model assessment (HOMA), the summation of insulin (ΣIRI), plasma renin activity (PRA) or 24 h norepinephrine excretion (24hU-NE) were observed between the hypertensive (HT) group (n =31) and normotensive (NT) group (n =71) before weight loss, but the basal serum leptin was significantly higher in the HT (16.8±1.1 ng/ml) than in the NT group (15.2±0.8 ng/ml), after adjusting for abdominal total fat. After a 3 month weight reduction program, the total abdominal fat, serum leptin and ΣIRI significantly decreased in both groups. The systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 144/84 to 130/77 mmHg only in the HT but not in the NT group. The PRA decreased in both groups, while the 24hU-NE significantly decreased only in the HT group. The changes in the leptin level were significantly correlated with the changes in both ΣIRI and HOMA after weight loss in the two groups, respectively. Finally, a statistically significant positive correlation was observed between the changes in the leptin and the changes in the mean blood pressure (MBP) (r =0.412, p <0.05) only in the HT group. Multiple regression analysis revealed that the changes in MBP were independently associated with the changes in 24hU-NE and the changes in either ΣIRI or HOMA in all subjects. However, a statistically significant positive correlation was observed between the changes in MBP and the changes in leptin levels even after adjusting for the total abdominal fat, 24hU-NE and either ΣIRI or HOMA (both expressed as a percentage of the baseline value) in a multiple regression analysis only in the HT group. These results suggest that leptin may play a role in the pathophysiology of obese hypertension. (Hypertens Res 2002; 25: 881-886)