Rat adipose tissue is the principal site of leptin synthesis, however, leptin gene expression has been demonstrated in many rat tissues. Some data indicate that leptin produced by human brain and adipose tissue could cooperate in the regulation of food intake. In this case the regulation of leptin gene expression in hypothalamus and in adipose tissue should be coordinately regulated. Food restriction is often undertaken by many humans trying to lose body weight. Thus, the current study was aimed to analyze whether leptin gene expression in rat hypothalamus and in adipose tissue is regulated synchronously by prolonged food restriction and prolonged food restriction/refeeding. We demonstrate here that although leptin gene is expressed at very low level in rat hypothalamus, its expression in hypothalamus was down-regulated by prolonged food restriction similarly as in the white adipose tissue. Refeeding after prolonged food restriction caused both an increase of leptin gene expression in white adipose tissue and the increase in serum leptin concentration. In contrast, no significant effect of prolonged food restriction/refeeding on hypothalamic leptin gene expression was observed. The reduction of leptin gene expression in both hypothalamus and white adipose tissue by prolonged food restriction was associated with a significant increase of NPY gene (a target of leptin signaling) expression in hypothalamus. Refeeding after prolonged food restriction caused the decrease of NPY gene expression in hypothalamus, however NPY mRNA level remained higher than in controls. The results presented in this paper indicate that prolonged food restriction/refeeding differentially affects leptin gene expression in adipose tissue and in hypothalamus. Moreover, obtained data suggest that in rats leptin synthesized in hypothalamus exerts marginal effect on NPY gene expression and on serum leptin concentration.