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Background: The polyol pathway hypothesis is the probable mechanism for the pathogenesis of diabetic complications, including neuropathy. Administration of tolrestat, one of the inhibitor of aldose reductase, the enzyme of rate-limiting step of polyol pathway, has been reported to improve most symptoms and signs of diabetic peripheral polyneuropathy, To evaluate the effectiveness and safety of tolrestat. We performed the randomized, placebo-controlled, doubleblind 24-week trial. Methods: Thirty-four patients with non-insulin dependent diabetes who had suffered from diabetic peripheral polyneuropathy for more than 3 months were randomized to placebo or tolrestat for 24 weeks. Twelve of placebo group and sixteen of tolrestat group completed the study. Symptoms of peripheral polyneuropathy, vibration perception thresholds, fasting glucose level, serum hemoglobin Al, serum routine chemistry were measured before and after the treatment. Results: In tolrestat group, the pain of diabetic peripheral polyneuropathy were significantly ameliorated and there was a trend toward reduction in vibration perception thresholds after the treatment. In placebo group, however, no significant changes of the pain and vibration perception thresholds were observed during the same period. During the treatment period, no significant changes in fasting glucose level, hemoglobin A1, or serum routine chemistry results were found in both groups. Of 19 cases of tolrestat group, 2 experienced mild postprandial epigastic discomfort, which disappeared spontaneously with continuing medication. Conclusion: With the 24-week treatment of tolrestat, the symptoms of diabetic peripheral polyneuropathy were significantly improved without any serious side effects.