This study examined the effects of an aldose reductase inhibitor, Sorbinil, on neuropathy over a 6-month period in streptozotocin-diabetic rats. Sorbinil treatment prevented the 10-fold increase in nerve sorbitol found with diabetes. It produced a 60% improvement in tibial nerve motor conduction velocity after 6 months. Morphometric profiles of nerves were also normalized. Axon area was reduced by 14% in untreated diabetic rats compared to age-matched controls, whereas Sorbinil-treated animals showed normal age-related axon growth. Myelin area was increased by 28% in untreated diabetic animals, but was the same as age-matched controls with Sorbinil treatment. Nerve myo-inositol levels were reduced by 45% after three months of untreated diabetes, but were normal after six months. Sorbinil treatment tended to restore myo-inositol levels toward normal over the shorter time period. It was concluded that axon growth retardation is the most likely cause of the conduction deficit seen in long-term experimental diabetes.