Abstract: Diabetic foot ulcers (DFU) represent a severe complication arising in diabetic patients due to prolonged poor glycemic control. The occurrence and progression of DFU are closely associated with interleukin-6 (IL-6) mediated inflammation. By activating signaling pathways such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and the mitogen-activated protein kinase (MAPK) pathway, IL-6 exacerbates insulin resistance, nerve damage, and vascular lesions, while promoting the release of inflammatory factors like tumor necrosis factor-α and C-reactive protein, thereby participating in the wound repair process. Under certain circumstances, IL-6 can also facilitate the healing of DFU wounds through its anti-inflammatory effects. This paper systematically elucidated the "spatiotemporal specificity" role of IL-6 in DFU, established an IL-6 mediated inflammation-related regulatory network and its role in risk prediction, and summarized the therapeutic potential of targeting IL-6, with the aim of providing references for the efficient clinical diagnosis and treatment of DFU.