Objective To investigate the efficacy of plantamajoside(PMS)on diabetic peripheral neuropathy(DPN)and to explore its mechanism of action from mitochondrial autophagy.Methods Mice(C57BL/6J)were randomly divided into 6 groups(n=10):normal group(Control),model group(Model),positive drug group(LA),and low(L-PMS),medium(M-PMS),and high(H-PMS)dosage groups.High-sugar and high-fat diet with intraperitoneal injection of streptozotocin was used to duplicate the DPN model.After successful model duplication,the intervention was administered by gavage for 4 weeks.Sciatic nerve was taken,and pathological changes were observed by HE and Nissl staining;oxidative stress indexes SOD,MDA,GSH-Px and inflammatory factors such as IL-1β,IL-6,TNF-αin sciatic nerve tissues were detected by kits,and the expression of VDAC1,TOM20,COX IV,PINK1,Parkin,and autophagy proteins of Beclin1,LC3,P62 in mouse sciatic nerves was detected by Western blotting.Results PMS dose-dependently improved the behavioral indexes of DPN mice,reduced the pathological damage of sciatic nerve,and resulted in tightly arranged sciatic nerve fibers,clearly visible myelin structure,uniform coloration,and increased number of Schwann cells as well as Nissl bodies.Compared with the model group,both the M-PMS group and the H-PMS group increased the expression levels of SOD and GSH-Px(P<0.05),while decreased the expression of MDA(P<0.05);the M-PMS group and the H-PMS groups reduced the expression of IL-1β,IL-6,and TNF-α(P<0.05);the L-PMS group,M-PMS group,and H-PMS group reduced the expression levels of VDAC1,TOM20,and COX IV proteins(P<0.05);the L-PMS group,M-PMS group,and H-PMS group could differentially increase the expression of PINK1,Beclin1,Parkin,and LC3 proteins(P<0.05),and decrease the expression of P62 proteins(P<0.05).Conclusion PMS can play a role in ameliorating neurological injury in DPN mice by promoting PINK1/Parkin pathway-mediated mitochondrial autophagy and alleviating oxidative stress-related inflammatory injury.