Objective To investigate the expression and clinical significance of serum C-C motif chemokine ligand 11(CCL11)and phosphorylated neurofilament heavy chain(pNF-H)in diabetic peripheral neuropathy(DPN).Methods A total of 174 patients with type 2 diabetes mellitus(T2DM)were enrolled as T2DM group,and 87 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.The T2DM patients were divided into DPN group and non-DPN group based on the occurrence of DPN.According to the disease severity[assessed by the Toronto Clinical Scoring System(TCSS)],DPN patients were further classified into mild DPN group,moderate DPN group and severe DPN group.Enzyme-linked immunosorbent assay was used to measure the levels of CCL11 and pNF-H.Pearson correlation analysis was employed to examine the correlations of serum CCL11 and pNF-H levels with TCSS scores in DPN patients.Multivariate uncon-ditional logistic regression analysis was conducted to screen for influencing factors of DPN in T2DM pa-tients.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of serum CCL11 and pNF-H levels for the development of DPN in T2DM patients.Results The serum levels of CCL11 and pNF-H in the T2DM group were significantly higher than those in the control group(P＜0.05).The incidence of DPN in the T2DM group was 47.13％(82/174).The age of the DPN group was significantly older,the disease course was significantly longer,and the levels of fasting blood glucose,HbA1c,CCL11 and pNF-H were significantly higher than those of the non-DPN group(P＜0.05).The serum levels of CCL11 and pNF-H increased sequentially from the mild DPN group to the moderate DPN group and then to the severe DPN group,with statistically sig-nificant differences(P＜0.05).Serum CCL11 and pNF-H levels in DPN patients were positively correlated with TCSS scores(r=0.661 and 0.619;P＜0.001).A prolonged disease duration,high glycated hemoglobin levels,high CCL11 levels and high pNF-H levels were independent risk factors for DPN in T2DM patients(P＜0.05).Thearea under the ROC curve for the combined pre-diction of DPN in T2DM patients by serum CCL11 and pNF-H levels was 0.861,which was greater than those for the individual indicators by serum CCL11(0.751)and pNF-H(0.765)levels(P＜0.05).After 1,000-time bootstrap internal validation through self-sampling,the C-index for the combined prediction was 0.861.Conclusion Elevated serum levels of CCL11 and pNF-H are in-dependently associated with the development of DPN in T2DM patients and increase with the worse-ning of DPN.The combination of these two markers has a high predictive value for DPN in T2DM patients.