Diabetic neuropathy typically presents as an insidious symmetrical distal degenerative disease of peripheral nerves. A failure of neurotrophic factors to regulate neuronal phenotype might be expected to result in such a clinical picture. Experimentally, diabetic rats show reduced expression of target-derived nerve growth factor as well as reduced expression of neuronal genes that are responsive to nerve growth factor. The latter is corrected by administration of exogenous nerve growth factor. Thus, deficient neurotrophic support might contribute to the pathogenesis of diabetic neuropathy, and any successful treatment might include exogenous neurotrophins or other strategies to correct their deficiency of action.