Objective To analyze the relationship between 25 hydroxyvitamin D［25-(OH)D］, serum IL-6 levels and diabetic peripheral neuropathy in Type 2 Diabetes Mellitus (T2DM) patients. Methods A total of 102 patients with T2DM or T2DM combined with DPN who were hospitalized in Department of Endocrinology of our hospital from September 2020 to September 2023 were selected as the study objects. They were grouped according to whether they were combined with DPN or not, including 50 cases in DPN group and 52 cases in SDM group (T2DM alone). General data, islet function indexes, related glucose metabolism indexes, 25-(OH)D level and serum IL-6 level of the two groups were collected and compared between the two groups. Multiple Logistic regression analysis was carried out with DPN as the dependent variable and the different index factors between the two groups as the independent variables. Results Body weight and abdominal circumference in DPN group were significantly lower than those in SDM group (P<0.05). The HBA1c level in DPN group was higher than that in SDM group, and the FCP and ALB levels were lower than those in control group (P<0.05). The level of IL-6 in DPN group was higher than that in SDM group, and the level of 25-(OH)D was lower than that in control group (P<0.05). ALB, 25-(OH)D and IL-6 were independent risk factors for T2DM combined with DPN, among which 25-(OH)D was negatively correlated with T2DM combined with DPN, while ALB and IL-6 were positively correlated with T2DM combined with DPN. Conclusion 25(OH)D and IL-6 are correlated with peripheral neuropathy in patients with type 2 diabetes, and the detection can help the clinical formulation of reasonable treatment plan, and will help to improve the prognosis of patients