Aim: To investigate the change in adipokine profile as a consequence of a combined dietand- exercise program. Methods: In the SLIM study, 98 men and women with impaired glucose tolerance (IGT) were randomized to a combined diet-and-exercise intervention (47 INT) or control program (51 CON). At baseline and after one year, an oral glucose tolerance test, an exercise test (maximal aerobic capacity), anthropometry measurements and plasma analyses were performed. Results: After 1 year, BMI, 2-hr glucose concentration and HOMA-index for insulin resistance (HOMA-IR) were reduced, maximal aerobic capacity was increased. Adiponectin and resistin concentrations were not different between INT and CON. Leptin concentration was reduced (INT: -2.7 ± 0.9 ng/ml, CON: 0.3 ± 0.9 ng/ml, P = 0.02) and related positively to changes in body composition, fasting glucose and insulin, 2-hr glucose, total cholesterol, plasma triglycerides and HOMA-IR. The correlation with HOMA-IR (r = 0.61, P <0.001) remained significant after adjustment for changes in waist, adiposity, aerobic capacity and fat intake (r = 0.36, P <0.01), suggesting that improvements in lifestyle habits affect adipose tissue metabolism and/or leptin resistance in a positive way. One-year changes in adiponectin related inversely to changes in HbA1c after adjustment for the same parameters. Conclusions: Leptin concentrations, but not adiponectin or resistin, were markedly reduced after lifestyle improvements. Lifestyle improved the relationship between circulating leptin and adiponectin and metabolic parameters (HOMA-IR and HbA1C, respectively), independent of changes in adiposity. For resistin it is not clear yet which factors may affect circulating concentrations.