OBJECTIVE Adipokines play an important role in metabolic regulations. Obesity, diabetes, and renal disturbances affect adipokine profile by influencing their complex effects on metabolism. Our objective was to assess the effect of low-energy diet intervention on serum adiponectin, leptin, and resistin levels in diabetic nephropathy. METHODS Seventeen subjects with diabetes type 2 and nephropathy participated in the study. After estimation of individual resting metabolic rates by indirect calorimetry, diets introducing 20% energy deficit were applied. At baseline and after 2 months of dieting, the following parameters were measured: body composition by dual x-ray spectrometry and serum adiponectin (Adp), leptin (Lep), resistin (Res), insulin, urea, creatinine, glucose, glycosylated hemoglobin, C-reactive protein, and tumor necrosis factor-alpha concentrations. Homeostatic model assessment (HOMA) was used to quantify insulin resistance. RESULTS Total energy, protein, and fat intakes diminished significantly with intentional dieting. Significant decreases in total body fat mass (FM) and its percentage in body mass (FM%) and trunk and gynoid fat mass, as well as in serum resistin and tumor necrosis factor-alpha levels, were also observed. Responses of adipokines to dietary treatment varied individually. Generally, they were affected by FM. Alterations in Lep concentrations correlated negatively with baseline FM, FM%, and android and gynoid fat mass and positively with changes in intake of protein, carbohydrates, and total energy of the consumed diet. Changes in Adp were inversely related to FM after therapy. Alterations in Res concentrations correlated positively with android fat mass before therapy and initial Lep levels. Adiponectin was inversely related to HOMA index before and after treatment. CONCLUSIONS Low-energy diet applied in diabetic nephropathy may decrease serum resistin levels and inflammation. In addition, responses of all adipokines to dieting appear to be affected by body fat mass, especially android fat mass.