Liposuction is one of the more common elective surgical procedures in the US and is supposed to be on the increase. There are no reported studies specifically addressing the metabolic sequelae of liposuction in obesity. The aim of the present study was to investigate the role of large-volume liposuction on insulin resistance and circulating inflammatory markers in obese people. Thirty healthy premenopausal obese (body mass index (BMI) from 30 to 45) and 30 age-matched normal weight (BMI<25) women were studied. In obese women, insulin sensitivity, as measured by the Homeostasis Model Assessment (HOMA=fasting plasma glucose x fasting serum insulin divided by 25), as well as serum adiponectin, the novel adipocytokine with insulin sensitising properties, were significantly lower, as compared with nonobese women (p<0.01), indicating insulin resistance; on the contrary, serum concentrations of the proinflammatory cytokines IL-6, IL-18 and TNF-alpha, as well as the sensitive marker of inflammation C-reactive protein, were significantly higher (p<0.01). All obese women were submitted to a single large volume liposuction (superwet technique): the mean aspirate volume was 3540 ml (range 2550-4670), corresponding to a net lipid loss of 2.7+/-0.7 kg (mean+/-SD). After six months of stable body weight after liposuction, women were less insulin resistant (p<0.05), had reduced concentrations of IL-6, IL-18, TNF-alpha and CRP (p<0.05-0.02), and increased serum levels of adiponectin (p<0.02) and HDL-cholesterol (p<0.05). There was a significant correlation between the amount of fat aspirate and changes in HOMA (r=0.28, p<0.05), TNF-alpha (r=0.31, p<0.02), and adiponectin (r=-0.34, p<0.02), as well as between the decrease in TNF-alpha and the increase in adiponectin after the surgical procedure (r=-0.45, p<0.01). Our study demonstrates that liposuction is safe and free of metabolic sequelae in obese women, pending a careful screening of the patient. Moreover, it is associated with amelioration of insulin resistance and reduced circulating markers of vascular inflammation which may help obese subjects to reduce their cardiovascular risk.