Abstract OBJECTIVE: The hypothalamus-hypophysis-thyroid axis may influence the secretion and metabolism of leptin. The aim of the study was to assess the effect of hypothyroidism and hyperthyroidism on serum leptin levels and adipocyte leptin mRNA expression. METHODS: Hypo-and hyperthyroidism were induced in rats by administering methimazole and L-thyroxine respectively. The serum levels of leptin, T3, T4 and TSH, body weight and adipocyte leptin mRNA expression were measured 10 days after methimazole or L-thyroxine administration and withdrawal respectively. Ten normal rats treated with normal saline served as the Control group. RESULTS: Serum leptin levels in rats with hypo- and hyperthyroidism and the Control group were correlated with body weight 10 days after administration (r= 0.84, 0.83, and 0.94 respectively; P< 0.05). After the effect of body weight had been factored out, serum leptin levels and adipocyte leptin mRNA expression in the rats with hyperthyroid 10 days after either administration or withdrawal were not different from the Control group. Ten days after administration, hypothyroid rats showed significantly decreased leptin levels and adipocyte leptin mRNA expression in comparison with those of 10 days after withdrawal ( 0.68± 0.07 ng/nl vs 1.98± 0.09 ng/ml and 0.39± 0.02 vs 0.87± 0.05, respectively; P< 0.05) and in comparison with the Control group ( 2.14± 0.46 ng/ml and 0.95± 0.03; P< 0.05). CONCLUSIONS: Thyroid hormone may play a role in maintaining a steady secretion of leptin.