The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.