Background Our aim was to investigate the regulation of the gene expression of leptin in subcutaneous adipose tissue biopsies in morbid obesity before and after biliopancreatic diversion (BPD). Methods Longitudinal study in morbidly obese subjects investigated twice: before and 6 months after BPD. Fourteen morbidly obese women, 37±13 years old and with a body mass index of 51.6±8.2 kg/m², were studied before and 6 months after BPD (40.6±8.0 kg/m²). Using reverse transcriptase polymerase chain reaction analysis, the mRNA expression of leptin was investigated in adipose tissue. Plasma leptin was measured by radioimmunoassay; plasma insulin was measured by microparticle enzyme immunoassay. Free fatty acids (FFA) were measured using a colorimetric kit. Results A significant decrease in leptin mRNA level was observed in comparison with pretreatment in BPD patients (59±34 vs 143±85 arbitrary units, P <0.01). A strict relationship between adipose tissue leptin mRNA and plasma leptin either before ( R²=0.80, P <0.0001) or after BPD ( R²=0.86, P <0.0001) and between plasma FFA concentration and insulin either before ( R²=0.65, P <0.001) or after BPD ( R²=0.92, P <0.0001) was observed. Finally, a significant correlation was found between changes in FFA and insulin ( R²=0.64, P <0.001), insulin and leptin ( R²=0.88, P <0.0001), and insulin and leptin mRNA ( R²=0.83, P <0.0001). Conclusion These data demonstrate a high correlation between leptin mRNA expression in adipose tissue and plasma leptin in postobese subjects after BPD. The significant relationship between both leptin mRNA and plasma leptin with insulin suggests that circulating insulin might regulate leptin expression. It might be hypothesized that plasma FFA concentration can act on the insulin secretion and subsequently on the leptin secretory pathway.