BACKGROUND: Oxidative stress plays a crucial role in the pathogenesis of diabetic peripheral neuropathy. Melatonin is one of the most powerful antioxidant substances and its role in the pathogenesis of diabetes has been the focus of much research. However, no data exist on melatonin levels in diabetic peripheral neuropathy. We investigated how levels of urinary 6-sulfatoxymelatonin, the main metabolite of melatonin, differed in diabetic peripheral neuropathy. METHODS: A total of 127 participants were enrolled into 3 groups: diabetic neuropathy (n=43), diabetes but no neuropathy (n=44), and controls (n=40). Neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. Melatonin level was evaluated by measuring 24-hour urine 6-sulfatoxymelatonin levels. RESULTS: We found significant differences in urinary 6-sulfatoxymelatonin levels between the 3 groups (p=0.023). The distribution of 6-sulfatoxymelatonin among all diabetic participants was significantly lower than in the control group (p=0.006). However, there was no difference in diabetics with and without neuropathy (p=0.792). 6-sulfatoxymelatonin levels were negatively and weakly correlated with plasma glucose(r = -0.211, p=0.017) and positively and weakly correlated with microalbuminuria (r= 0.209, p=0.023). Regression analysis was found a significant relationship between age (B = 0.826, 95% Cl=0.227 to 1.426), insulin use (B = 14.584, 95% CI= 3.857 to 25.311), glomerular filtration rate (B = 0.248, 95% CI= 0.018 to 0.478) and 6-sulfatoxymelatonin levels. 6-sulfatoxymelatonin levels in insulin users were significantly higher than they were in nonuser diabetics (p=0.001). CONCLUSION: Urinary 6-sulfatoxymelatonin levels were lower in diabetics but the presence of neuropathy did not affect 6-sulfatoxymelatonin levels. Insulin may improve melatonin levels in diabetics.