Both thyroid hormones and leptin affect sympathetic nervous system activity, basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one also affects the actions of the other. We examined the alterations in serum leptin concentrations and leptin mRNA expression in hypothyroid rats and investigated the relation between serum leptin and leptin mRNA levels with the total adipose tissue mass and total body weight. Twenty male Wistar rats were divided into 2 groups, euthyroid and hypothyroid. Their body compositions were examined by Dual Energy X-ray Absorptiometry at the beginning and end of the study. Serum leptin concentrations and levels of leptin mRNA in the retroperitoneal white adipose tissue were measured at the end of the study. Serum leptin concentrations did not show any difference between the two groups (1.9 +/- 0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the hypothyroid rats were lower than the euthyroid rats (21.1 +/- 2.5 g in the euthyroid group and 14.2 +/- 1.9 g in the hypothyroid group, P > 0.05 between groups at the end of the study) although the difference between the groups was statistically not significant. Leptin mRNA level was significantly higher in the hypothyroid group than in the euthyroid group (21.6 +/- 1.6 vs. 15.1 +/- 1.2 ng respectively, P = 0.002) although the dissected retroperitoneal fat weight was significantly lower in the hypothyroid group versus the euthyroid group (1.0 +/- 0.2 vs. 1.8 +/- 0.2 g respectively, P = 0.013). In conclusion, the change of leptin mRNA expression in white adipocytes was thought to be the direct result of hypothyroidism or a compensatory response to metabolic changes caused by hypothyroidism.