Increased resistance to ischemic nerve conduction failure (RINCF) has been demonstrated in the spontaneously diabetic BB Wistar rat as well as in non-insulin dependent but hyperglycemic litter-mates. There is marked variability in the severity of the ischemic resistance in insulin dependent rats but not in the non-insulin dependent litter-mates suggesting that the administration of insulin could acutely alter RINCF. We therefore studied the effects of rapid normalization of the blood glucose on RINCF in diabetic rats. Injection of insulin produced a rapid fall in blood glucose to normal levels by 2 h. This was closely followed by a significant fall in RINCF which reached normal levels by the time that the blood glucose had been normal for 2 h. These results suggest that increased RINCF in diabetes is a function of the availability of substrate for energy metabolism which is directly related to the blood glucose concentration and underscores the importance of measuring the blood glucose level whenever measurements of nerve function are made.