We studied resistance to ischemic nerve conduction failure (RINCF) following rapid alterations of blood glucose in normal and diabetic rats. We measured RINCF hourly for 4 hours in normal and diabetic rats. We then made normal rats hyperglycemic and diabetics euglycemic. In normal rats, we measured RINCF sequentially for 4 hours immediately after glucose injection and once after 1,2,3, or 4 hours of hyperglycemia. In diabetics, we measured RINCF sequentially for 4 hours after insulin injection. In normal rats, in sequential measurements, RINCF progressively fell but glucose injection prevented this fall. Hyperglycemia without preceding ischemia increased RINCF. In diabetic rats, sequential measurements also produced a decline in RINCF, accentuated with insulin injection. The results suggest that both glucose and insulin are important in determining the response of peripheral nerve to ischemia. They also underscore the importance of knowing the blood glucose and time of most recent insulin injection when measuring RINCF.