The effects of angiotensin-converting enzyme (ACE) inhibition with perindopril on renal vascular structure were studied in control and streptozotocin diabetic male Sprague-Dawley rats after 3 weeks. After kidneys were perfusion-fixed at systolic blood pressure, morphometric analysis of vascular structural changes in the media of the renal vasculature at the cortico-medullary junction was performed. Vascular hypertrophy was present in the diabetic vessels, as assessed by an increase in medial cross-sectional area for a given lumen size. This relative increase in medial area was prevented by perindopril treatment, consistent with an antitrophic effect on diabetic kidney vessels by ACE inhibition. The diabetic kidney had an increased proportion of small vessels less than 50 μm diameter at the cortico-medullary junction, perhaps representing diabetes induced angiogenesis. This subpopulation of vessels was reduced in number after perindopril treatment. Our data support a role for increased activity of angiotensin converting enzyme as a mechanism for vascular hypertrophy, which may be involved in the pathogenesis of diabetic vasculopathy and nephropathy.