Aim: Appetite control is an important goal for the management of non-alcoholic fatty liver disease, diabetes mellitus and obesity; however, little is known about how hormones concerning appetite regulation are affected by long-term consumption of a high-fat diet. We investigated the effect of high-fat diet on secretory regulation of ghrelin and leptin in rats.Methods: Rats were fed a control or a high-fat diet for 18 weeks and then killed. Before being killed, a glucose tolerance test was performed. Weight, total calorie intake and blood glucose levels were measured, and the plasma levels of total and active ghrelin, and leptin were analyzed by enzyme-linked immunosorbent assay.Results: Body and fat weight and total calorie intake were significantly higher in the high-fat diet group than in the control, although blood glucose levels did not differ. Plasma leptin was significantly higher in the high-fat diet group, and a significant positive correlation was observed between bodyweight and leptin levels in both groups. The levels of active and total ghrelin were not significantly changed by high-fat diet, and active ghrelin levels in the control group significantly correlated negatively with bodyweight, while its correlation was lost in the high-fat diet group. The glucose tolerance test showed that ghrelin levels were significantly higher than those of controls even 60 min after glucose loading. Conclusion:These results indicate that secretion of ghrelin, but not leptin, are deranged by consumption of a high-fat diet, and active ghrelin levels lose their correlation with bodyweight and food intake.