Background and Aims: There are few studies addressing the effect of weight loss on circulating levels of adipocytokines. The aim of our study was to determine whether different diets would have different weight loss effects and to examine the changes in adipocytokine levels. Methods: A population of 90 obesity non-diabetic outpatients was analyzed in a prospective way. The patients were randomly allocated to two groups: (a) diet I (low-fat diet), and (b) diet II (low-carbohydrate diet). At baseline and after 3 months on the diet, adipocytokines were evaluated. Results: 43 patients were randomized to group I and 47 patients to diet group II. No differences were detected between weight loss in either group (3.3 ± 0.51 vs. 4.4 ± 0.6 kg; n.s.). In group I, a significant decrease in leptin levels was found. In group II, leptin and C-reactive protein (CRP) levels also decreased. The decrease in leptin levels was lower with diet I than II (16.4 vs. 22.8%; p < 0.05). Conclusion: The serum leptin concentration decreased due to the 3-month intervention with low-fat and low-carbohydrate diets, without changes in other adipocytokines. The decrease in leptin and CRP levels were higher with a low-carbohydrate diet than a low-fat diet.