Introduction: Brain Natriuretic Peptide (BNP) is secreted from cardiac myocytes in response to the wall stress. BNP is eliminated via Natriuretic Peptide Receptor C (NPR-C) and degradation by extracellular proteases including neprilysin (NEP). Obesity and insulin resistance predispose to lower circulating natriuretic peptide levels. Raised NEP activity and an elevated NPR-C gene expression have been described in obese individuals with insulin resistance and lower circulating levels of natriuretic peptide. Methods: We assessed the relationship between markers of peptide production and pulmonary clearance with indices of insulin resistance and body weight. The cardiac, peripheral and pulmonary Extraction Ratio (ER) has been quantified to assess BNP synthesis and clearance. Twenty one individuals admitted for EP study were consented. Simultaneous sampling of serum BNP level was performed from femoral artery and vein, coronary sinus and femoral artery and pulmonary artery and pulmonary wedge position. Results: The mean serum BNP level was 37 ng/L. The mean cardiac ER was 1.20, pulmonary and peripheral ER was 0.13. There was a tendency for lower cardiac and pulmonary ER in males. Pulmonary ER correlated with age (r=0.495, p=0.023) and systolic BP (r=0.58, p=0.006) only. However there was no correlation between cardiac and pulmonary ER with BMI, waist circumference and HOMA-IR. Conclusions: We found no correlation between the marker of BNP pulmonary clearance with body size and insulin resistance. Induction of the adipose tissue specific NPR-C pathway (rather than NEP clearance) is more likely the cause of the lower level of BNP in patients with obesity and insulin resistance.