In this study, we aimed to evaluate the possible relations of serum leptin and thyroid hormones on insulin treatment of surgically thyroidectomized and streptozotosin induced diabetic group of rats and whether the thyroid hormones control the leptin levels or leptin levels affect the thyroid hormones in DM. The Sprague–Dawley rats were assigned to eight groups: group 1, control; group 2, diabetes (injected intraperitoneally (i.p.) with streptozotocin (stz) 55 mg/kg); group 3, diabetes + insulin (rats were treated with insulin, 7–10 U/kg/day, subcutaneously); group 4, surgically thyroidectomized control; group 5, thyroidectomized + diabetes (3 weeks after the surgical operation, injected i.p. with stz); group 6, thyroidectomized + diabetes + insulin; group 7, thyroidectomized + diabetes + insulin + thyroid hormone (after diabetes induction, rats were treated with insulin and thyroid hormone, levothyroxin sodium (T4; 2.5 μg/kg); group 8, thyroidectomized + diabetes + insulin + thyroid hormone (T4; 5 μg/kg). The free and total T3 and T4 levels were measured in serum samples by otoanalyzer, and leptin levels were determined by ELISA method. The main finding of our recent study is that the decreased levels of serum leptin during the diabetes, hypothyroidism, and hypothyroidism with diabetes can be regulated in different percentages with the treatment of insulin and various doses of thyroid hormone. The observations in our study suggest the idea that during diabetic hypothyroidism, without thyroid hormone treatment, insulin is not sufficient to balance the metabolic pathways so mediated effects of insulin in leptin regulation via thyroid hormones are an increased possibility.