The arcuate nucleus (AN) of the hypothalamus is a key area in which endocrine messages are relayed to the brain, while midbrain raphe nucleus (RN) is the source of brain serotonin. Both nuclei contribute to the central mechanism of energy homeostasis. This experiment aimed to determine the impact of AN and RN grafts on insulinemia and obesity in diabetic rats. AN and RN were dissected from 15-day (Fa/Fa) lean embryos and grafted separately or together into the third brain ventricle of obese (fa/fa) male Zucker rats. Histological analysis showed the functional maturity of grafts, which were vascularized, contained neurons reinnervating the periventricular hypothalamus and hypophysis, and expressed neuropeptide Y and enzymes for dopamine and serotonin synthesis. Three months after transplantation, the rats grafted with AN or RN had a lower body weight gain compared to sham-operated rats (19% and 17%, respectively). Rats grafted with AN together with RN gained significantly less body weight than rats grafted with AN or RN separately (31% vs. sham-operated rats), and showed a decreased plasma insulin concentration (132 ± 33 μU/ml) vs. sham-operated rats (459 ± 108 μU/ml, p < 0.05). A synergistic effect on alleviating obesity and insulinemia by double AN and RN grafts suggests that both these nuclei are functionally interrelated in maintaining energy homeostasis, and normal functioning of both nuclei is altered during obesity.