Objective To investigate the application of high?frequency ultrasound for the diagnosis of diabetic peripheral neuropathy （DPN）. Methods A total of 141 diabetic patients were selected and divided into diabetic peripheral neuropathy group （DPN group，n = 44），diabetic group （DM group，n = 56） and non?diabetic group （NDM group，n = 41）. The cross?sectional area （CSA） of the sciatic， tibial， common peroneal， posterior tibial and median nerves were measured by high?frequency ultrasound in each group， and the Michigan Neuropathy Screening Instrument （MNSI） and the Toronto Clinical Scoring System （TCSS） were applied to assess peripheral nerve function in patients in the DM and DPN groups. The ROC curves were used to analyze the value of peripheral nerve cross?sectional area （CSA） in the diagnosis of DPN. Results Compared with the NDM and DM groups， the measured sciatic， tibial， and posterior tibial nerve CSA was significantly greater in the DPN group （P < 0.05）； he MNSI scores was significantly higher in the DPN group compared with the DM group （P < 0.05）， CSA was positively correlated with the MNSI score and TCSS score （P < 0.05）；ROC curve analysis showed that the posterior tibial nerve CSA had a significant predictive value in the diagnosis of DPN. Conclusion The CSA of sciatic nerve， tibial nerve， and posterior tibial nerve measured by high?frequency ultrasound was significantly greater in the DPN group compared with the DM and NDM groups. CSA correlated well with MNSI scores and TCSS scores. High?frequency ultrasound?measured CSA of the sciatic， tibial， and posterior tibial nerves has potential value in the diagnosis of DPN.