Obestatin is a gastric derived 23 amino acid peptide, which has shown anorectic effects in a number of experimental paradigms after both peripheral and central administration. On the other hand, several researchers were not able to confirm these data. Since all previous experiments have been performed in animals fed a standard laboratory diet, we studied obestatin effects in male Wistar rats fed both a standard laboratory chow (STD) diet (3.5% fat, 63% carbohydrate, 14% protein, 19.5% other components without caloric value; 3.20 kcal/g) and a highly palatable cafeteria-style (CAF) diet (30% fat, 56% carbohydrate, 14% protein; 4.20 kcal/g). Vehicle or obestatin (10, 50 or 100 nmol/kg) was injected intraperitoneally daily for 12 days. In STD diet rats, obestatin decreased daily caloric intake and body weight gain compared to vehicle treated rats. The anorectic and weight reducing effects of obestatin treatment were evidenced since day 6 and day 8 of treatment, respectively, and were consistent through the end of treatment. On the other hand, in CAF diet rats, obestatin treatment did not modify either daily caloric intake or body weight gain. In CAF diet rats, the percentage intake from standard food was decreased, balanced by an increase in cafeteria food intake. Obestatin treatment affected neither water consumption nor the intake of any specific food within the cafeteria diet. In conclusion, obestatin decreases caloric intake and body weight gain, but only in rats fed a STD diet.