Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARγ agonists decrease leptin levels. However, the effects of PPARα agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARγ agonist rosiglitazone (RSG) and PPARα agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 ± 19 vs. 207 ± 34 mg/dl, 58 ± 20 vs. 112 ± 23 mg/dl, 3.1 ± 1.0 vs. 15.2 ± 4.0 ng/ml, 1.6 ± 0.5 vs. 3.6 ± 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 ± 19 vs. 207 ± 34 mg/dl, 57 ± 16 vs. 112 ± 23 mg/dl, 4.3 ± 2.1 vs. 15.2 ± 4.0 ng/ml, 1.6 ± 0.4 vs. 3.6 ± 1.6 ng/ml, respectively). These results suggest that PPARα agonists may decrease serum glucose, insulin and leptin levels as PPARγ agonists do in diet-induced obese rats.