Neuropathy is one of the typical features of chronic complications of diabetes mellitus. Recent analyses indicate that subjects with impaired glucose tolerance (IGT) already have disturbance of peripheral nerve function. To test the role of adipocytokines, that tend to be abnormal in IGT subjects, on diabetic neuropathy, we analyzed the relationship between plasma adipocytokine levels (TNFalpha, adiponectin, and leptin) and nerve conduction velocity in 105 type 2 diabetic subjects (M/F = 66/39, age = 60.8 +/- 11.8 years, BMI = 24.7 +/- 5.0kg/m2). Adipocytokines were measured by ELISA, and motor conduction velocity (MCV) and sensory conduction velocity (SCV) in median, ulnar, and tibial nerve were measured by electrical stimulation. Motor conduction velocity and SCV were corrected by age to be 1.0 as the normal value, and the average of three nerves were used to be the representative value. Relationship between corrected MCV or corrected SCV as a dependent variable and the duration of diabetes, HbA1C, BMI, TNFalpha, adiponectin, and leptin concentrations as independent variables were analyzed by multiple regression. Duration of diabetes and HbA1C were highly related with both corrected MCV (P < 0.02 and P < 0.001) and SCV (P < 0.02 and P < 0.05) by this analysis. Only corrected SCV was related significantly with TNFalpha (P < 0.05), and close to significantly with leptin (P = 0.059) concentrations. These results indicate that increased plasma glucose levels and duration of diabetes are the major factors that modulate diabetic neuropathy. However, nerve function may be affected by plasma cytokine levels like TNFalpha, and this effect was more significant on sensory nerves than motor nerves. The present results suggest that adipocytokines may play a role not only on angiopathy but also on neuropathy in diabetics.