Background:Diabetes is one of the most common causes of peripheral neuropathy. There are no known cures for diabetic neuropathy. Pentoxifylline could theoretically be a beneficial treatment for diabetic sensory neuropathy, but there is not enough evidence to prove its effect. The aim of this study was to investigate the effect of pentoxifylline on distal diabetic neuropathy.Materials and Methods:In this randomized double-blinded placebo-controlled trial, 60 patients with diabetic peripheral neuropathy were randomized into two groups. The intervention group received Vitamin B1 (100 mg twice daily) and pentoxifylline (400 mg twice daily) and control group received Vitamin B1 (100 mg twice daily) and placebo (twice daily) for 2 months. Before and after the intervention, the symptoms of distal polyneuropathy were recorded by the Michigan Neuropathy Screening Instrument. ANCOVA, Paired t-test, unpaired t-test, Chi-square, and Fisher's exact test were used to compare changes in symptoms and sign of distal polyneuropathy.Results:The mean age of patients was 57.1 ± 8.02 years. There was no significant difference between the two groups in regard to the baseline variables. Blood pressure, body mass index, and blood glucose did not change significantly during the study. In the pentoxifylline group, the symptoms of peripheral neuropathy were significantly improved, in comparison with placebo group (P = 0.042).Conclusion:This study showed pentoxifylline could be effective in reducing the symptoms of distal diabetic neuropathy.