The effects of minimal doses of insulin administered by intracerebroventricular (ICV) and intracisternal (IC) routes in mongrel dogs, on peripheral blood glucose level (BGL) have been studied. The dose of 0.1 U of insulin was found to be the minimal dose. This dose produced an immediate short lived hyperglycaemia followed by a marked and sustained hypoglycaemia. Both the effects were not observed in spinal cord transected-vagosympathectomised animals. The immediate hyperglycaemic effect was not observed in adrenalectomised animals whereas the subsequent hypoglycaemic effect did not appear only when the liver was removed. In an attempt to identify the precise site of action in the central nervous system (CNS), The cerebellomedullary angles were found to be the most sensitive sites for the action of locally applied insulin. It is suggested that insulin on central administration causes a rise in the BGL by an action on the adrenal glands and subsequently causes a marked fall in BGL by an action on the liver through some nerve fibers.