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Excitation of the insulin sensitive glucoregulator receptor in the central nervous system (C.N.S.) causes an immediate decrease in the systemic blood sugar level in rats. 2. A study was made in animals that were subjected either to evisceration or to evisceration and functional-hepatectomy, in order to assess the role of the liver and pancreatic hormones in the blood sugar decrease following insulin injection into the carotid artery. 3. The results indicate that the change in the systemic blood sugar level, induced by exposing the C.N.S. to insulin, was effected through a direct influence of the receptor centre on glucose metabolism of the liver. 4. Excitation of the insulin-sensitive receptor in the C.N.S. regulates carbohydrate metabolism of the liver, both by inhibiting hepatic glucose output and by facilitating hepatic glucose uptake. 5. The data derived from these animal models reveal that the mode of transmission of the impulse from the C.N.S. region is through efferent neural pathways that directly influence the hepatic carbocydrate metabolism, and not through a modification of pancreatic hormone secretion.