Objective: This study explored the changes in the levels of IL-6, IL-17, TNF-alpha, and TNF-beta, whether such changes were associated with anxiety and depression in diabetic peripheral neuropathy (DPN), and what factors associated with the occurrence of DPN. Methods: Forty-four patients diagnosed with DPN comprised the DPN group, including DPN1 (mild diabetic peripheral neuropathy, 29 cases) and DPN2 groups (moderate-severe diabetic peripheral neuropathy, 15 cases). Thirty-seven individuals with type 2 diabetes mellitus constituted the diabetes mellitus with no neuropathy (NDPN) group. Electromyography was applied to confirm DPN, and the Toronto clinical scoring system (TCSS) score was used to assess the severity of DPN. All subjects' emotions were evaluated using the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Triiodothyronine (T-3), tetraiodothyronine (T-4), and thyroid-stimulating hormone (TSH) levels were measured using chemiluminescent immunoassay. The relevant biochemical indicators were detected using an automatic biochemical analyzer. The plasma levels of cytokines were detected using quantitative sandwich enzyme-linked immunosorbent assay. Results: Patients with DPN had elevated levels of anxiety, IL-6, IL-17, and TNF-alpha. There were some positive associations between negative emotions and cytokines. The TCSS score positively correlated with IL-17, SAS score, and T3. DPN independently correlated with age, disease duration, fasting plasma glucose (FPG), and IL-17. The combination of IL-17 and TNF-alpha had higher diagnostic value for DPN than any single cytokine. Conclusion: Patients with DPN had elevated levels of inflammatory cytokines, which were associated with negative emotion, and IL-17 had independent correlation with DPN.