A study comparing ibuprofen (600 mg four times a day) vs sulindac (200 mg twice a day), and a placebo in the treatment of painful diabetic peripheral neuropathy was conducted in 18 male outpatients. Discomfort was characterized and rated with a subjective neuropathy score. The response to both ibuprofen and sulindac was better than it was to placebo in the entire group. There were no changes in glucose control or renal function. Further studies are necessary to evaluate the significance of aldose reductase-inhibitor properties of nonsteroidal anti-inflammatory drugs and to select the "best" one of these drugs for the treatment of diabetic neuropathy.