Zinc deficiency has been shown to result in poor appetite, causing anorexia. However, the role of zinc in the regulation of food intake is not well understood. In the present study, we hypothesized that zinc deficiency dysregulates circulating leptin level and leptin mRNA gene expression, and that whether these changes were occuring as a direct result of, or as a compensatory effect of zinc deficiency in rats. After an adaptation period of 4 weeks, Sprague Dawley rats were provided with three different level of zinc, as one week of a Zn-adequate (30 mg/kg) diet, then two weeks of a Zn-depletion (1 mg/kg ), and finally by two weeks of a Zn-repletion (50 mg/kg) diet. At the end of each dietary experimental period, one third of the 26 rats were killed. Zinc levels of blood subfractions (plasma, yee blood cells and mononuclear cells) and in the liver were substantially decreased, despite the fact that food intake was not substantially decreased during the Zn-depletion period. Serum leptin concentration was significantly increased during the zinc depletion period. Leptin mRNA in adipose tissue was also shown to be highly expressed during the Zn-depletion period. Presumably, increased leptin level and leptin mRNA induction during Zn-depletion conditions may be the cause of lowered appetite which is the common symptom of Zn-deficiency. In conclusion, These increases in circulating leptin levels and in leptin gene expression would be the direct result of, rather than the compensatory effect of, zinc deficiency.