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Diabetic Peripheral Neuropathy (DPN) is an extraordinary common complication of diabetes accounting for substantial suffering by predisposing the foot to ulceration and lower extremity amputation. Besides, it has also become a huge economic burden for patients and for the world. However, primary treatment trials have not yet provided appropriate therapies due to a poor understanding of the mechanisms underlying the disease. The currently well-accepted cause of the disease is hyperglycemia, while insulin resistance and dyslipidemia may also have impacts on it. Hyperglycemia contributes to oxidative stress in neurons and thus activates various biochemical pathways to damage the neural tissues. This review focuses on the 8 parimary biochemical mechanisms of DNP, namely polyol pathway, advanced glycation end-products pathway, PKC pathway, Poly(ADP-ribose) polymerase pathway, hexosamine pathway, oxidative stress and mitochondrial dysfunction, inflammation and growth factors, and dyslipidemia and insulin resistance, intending to provide a systemic mind for seeking the therapeutic targets for DPN.