The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid-binding protein (A-FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A-FABP were measured in 77 morbid-obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL-18), adiponectin, and high-sensitive C-reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated. After massive weight loss, A-FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P<0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow-up, was observed. A decrease in sTNFR2, IL-18, hsCRP, and an increase in adiponectin levels (P<0.001 in all cases) were observed after the gastric bypass. HOMA-IR index improved 1 year after surgery and after multiple regression analysis remained associated with A-FABP after controlling for confounding variables (beta=0.322, P=0.014; R2 for the model 0.281). In morbid-obese women, plasma A-FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA-IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A-FABP in the pathogenesis of insulin resistance in morbid obesity.