In type 2 diabetes mellitus (T2DM), the functions of the brain insulin system are impaired, which is associated with a decrease in insulin transport across the blood-brain barrier due to insulin resistance. To restore insulin deficiency in the brain, intranasally administered insulin (II) can be used, and its effect can be enhanced by intranasal administration of C-peptide (ICP). The aim of this work is to study the effect of ten-day treatment of male Wistar rats with hyperinsulinemic and normoinsulinemic T2DM with II (20 µg/rat/day), ICP (36 µg/rat/day) or II+ICP on metabolic and hormonal indices. Hyperinsulinemic T2DM was induced by a 3-month high-fat diet and low-dose streptozotocin treatment of adult rats, while normoinsulinemic T2DM was induced by high-dose streptozotocin treatment of 5-day-old pups. In hyperinsulinemic diabetic rats, II-monotherapy attenuated hyperglycemia, hyperinsulinemia, and hyperleptinemia, and partially restored the blood levels of fT4, tT4, and tT3 reduced in DM2 (p<0.05 as compared to untreated diabetes). ICP was not effective and, in the II+ICP group, it significantly reduced the restorative effects of II. In normoinsulinemic rats with T2DM, II monotherapy increased fT4 and tT3 levels by 31% and 26%, while ICP decreased glucose-stimulated leptin levels by 31% (p<0.05 as compared to untreated diabetes). The use of II+ICP attenuated hyperglycemia, reduced glucose-stimulated insulin levels, and restored the thyroid hormones levels to their control values. Thus, ICP and its combination with II are effective in restoring metabolic and hormonal indices in rats with normoinsulinemic T2DM, but do not improve them in rats with hyperinsulinemic T2DM.