The aim of this study was to test the efficacy of the aldose-reductase inhibitor Tolrestat in the treatment of carpal tunnel syndrome in Type 2 diabetic patients. Seventeen patients were treated with Tolrestat (200 mg daily for 12 months) clinical and neurophysiological evaluations were performed at baseline, 6 and 12 months; symptoms and blood glucose control were assessed at baseline, 2, 6, and 12 months. Thirteen Type 2 diabetic patients suffering from symptomatic carpal tunnel syndrome served as controls. Neurophysiological studies showed improvement in the sensory conduction velocity of the median nerve between forefinger and wrist (baseline 37.5 +/- 4.3 vs 6 months 41.3 +/- 5.7 ms-1, p < 0.0005 and baseline vs 12 months 41.4 +/- 8.2 ms-1, p < 0.005) but not between wrist and elbow. The terminal latency index of the median nerve was unchanged. Paraesthesiae and pain improved in terms of intensity and frequency. Blood glucose control was not significantly changed. We conclude that treatment of this case series with Tolrestat appears to produce beneficial effect on the outcome of carpal tunnel syndrome in diabetic patients.