Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, characterized by peripheral nerve dysfunction. Diabetic distal symmetric polyneuropathy (DSPN) is the most common form of DPN. The prevalence of DPN increases with the duration of diabetes, with up to 50% of patients with diabetes for over 10 years affected. Common clinical manifestations include pain, numbness, and paresthesia, and severe cases may lead to foot ulcers and amputation. The etiology and pathogenesis of DPN are not fully understood, but hyperglycemia, lipid metabolism disorders, and insulin signaling abnormalities are considered key factors. These factors disrupt the structure and function of the peripheral nervous system, including myelinated and unmyelinated nerve fibers, perikaryon, neurovascular, and glial cells. Abnormalities in the insulin signaling pathway inhibit axon repair and promote cell apoptosis. Recent studies have explored mechanisms such as oxidative stress, microvascular damage, and neuroinflammation in DPN. Understanding these mechanisms may help develop targeted screening and treatment strategies. The pathogenesis of DPN involves multiple pathways, including the protein kinase C (PKC) pathway, polyol pathway, advanced glycation end (AGE) pathway, hexosamine pathway, and PARP pathway. These pathways contribute to oxidative stress, inflammation, and mitochondrial dysfunction, leading to nerve damage. The PKC pathway is involved in glucose metabolism and can activate downstream pathways that cause nerve damage. The polyol pathway leads to sorbitol accumulation, which disrupts cell osmotic balance and causes oxidative stress. The AGE pathway promotes inflammation and oxidative stress through the activation of receptors and downstream signaling pathways. The hexosamine pathway is involved in glucose metabolism and can lead to oxidative stress and inflammation. The PARP pathway is associated with DNA repair and can contribute to oxidative stress and nerve damage. The insulin pathway plays a role in nerve growth and repair, but insulin resistance in T2DM can impair these processes. The Wnt/β-catenin, MAPK, mTOR, and TSH pathways are also involved in DPN pathogenesis. These pathways regulate cell proliferation, differentiation, and metabolism, and their dysregulation can contribute to nerve damage. Diagnosis of DPN includes clinical evaluation, sensory tests, and nerve conduction studies. Treatment involves strict blood sugar control, medication, and lifestyle modifications. Understanding the mechanisms of DPN is crucial for developing effective treatments.Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, characterized by peripheral nerve dysfunction. Diabetic distal symmetric polyneuropathy (DSPN) is the most common form of DPN. The prevalence of DPN increases with the duration of diabetes, with up to 50% of patients with diabetes for over 10 years affected. Common clinical manifestations include pain, numbness, and paresthesia, and severe cases may lead to foot ulcers and amputation. The etiology and pathogenesis of DPN are not fully understood, but hyperglycemia, lipid metabolism disorders, and insulin signaling abnormalities are considered key factors. These factors disrupt the structure and function of the peripheral nervous system, including myelinated and unmyelinated nerve fibers, perikaryon, neurovascular, and glial cells. Abnormalities in the insulin signaling pathway inhibit axon repair and promote cell apoptosis. Recent studies have explored mechanisms such as oxidative stress, microvascular damage, and neuroinflammation in DPN. Understanding these mechanisms may help develop targeted screening and treatment strategies. The pathogenesis of DPN involves multiple pathways, including the protein kinase C (PKC) pathway, polyol pathway, advanced glycation end (AGE) pathway, hexosamine pathway, and PARP pathway. These pathways contribute to oxidative stress, inflammation, and mitochondrial dysfunction, leading to nerve damage. The PKC pathway is involved in glucose metabolism and can activate downstream pathways that cause nerve damage. The polyol pathway leads to sorbitol accumulation, which disrupts cell osmotic balance and causes oxidative stress. The AGE pathway promotes inflammation and oxidative stress through the activation of receptors and downstream signaling pathways. The hexosamine pathway is involved in glucose metabolism and can lead to oxidative stress and inflammation. The PARP pathway is associated with DNA repair and can contribute to oxidative stress and nerve damage. The insulin pathway plays a role in nerve growth and repair, but insulin resistance in T2DM can impair these processes. The Wnt/β-catenin, MAPK, mTOR, and TSH pathways are also involved in DPN pathogenesis. These pathways regulate cell proliferation, differentiation, and metabolism, and their dysregulation can contribute to nerve damage. Diagnosis of DPN includes clinical evaluation, sensory tests, and nerve conduction studies. Treatment involves strict blood sugar control, medication, and lifestyle modifications. Understanding the mechanisms of DPN is crucial for developing effective treatments.