A deficiency in essential fatty acid metabolism has been widely reported in both human and animal diabetes. Fish oil supplementations (n-3 fatty acids), containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were less effective on diabetic neuropathy than (n-6) fatty acids. This partial effect of (n-3) fatty acids might be attributed to the presence of EPA, a competitor of arachidonic acid, which enhanced the diabetes-induced decrease of this fatty acid in serum and tissues. For determining whether a supplementation with DHA alone could prevent neuropathy in streptozotocin-induced diabetes, diabetic rats were given daily, by gavage, liposomes containing DHA phospholipids, at a dose of 60 mg/kg. Eight weeks of diabetes induced significant decreases in nerve conduction velocity (NCV), nerve blood flow (NBF), and sciatic nerve and erythrocyte (red blood cells [RBCs]) Na,K-ATPase activities. DHA phospholipids totally prevented the decrease in NCV and NBF observed during diabetes when compared with the nonsupplemented diabetic group. DHA phospholipids also prevented the Na,K-ATPase activity decrease in RBC but not in sciatic nerve. Moreover, DHA level in sciatic nerve membranes was correlated with NCV. These results demonstrate a protective effect of daily doses of DHA on experimental diabetic neuropathy. Thus, treatment with DHA phospholipids could be suitable for evaluation in clinical trials.