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Background: The purpose of this study was to establish the safety of negative pressure wound therapy (NPWT) in the treatment of acutely debrided, deep diabetic foot infections (DDFI) and to determine the value of insulin resistance in monitoring of treatment of these infections with negative pressure wound therapy.Methods: A group of 15 patients with DDFI treated by radical surgical debridement and simultaneous NPWT was prospectively studied.During the debridement, a deep tissue sample was obtained and sent for microbiological testing.The patients were followed clinically for 10 days and NPWT dressings were changed every 2 to 3 days or sooner when indicated.The peripheral blood samples were obtained before the radical debridement and 3 and 10 days afterwards and the concentrations of plasma insulin, glucose and cytokines were measured, Euglycemic□ Hyperinsulinemic Glucose Clamps were performed before the radical debridement and 3 and 10 days afterwards.The levels of phospho-tyrosine, phospho-serine307 of IRS-1 and phospho-JNK in muscle were analyzed with Immunoprecipitation and Western Blotting before the radical debridement and 3 and 10 days afterwards in diabetic patients with deep foot infection.Results: NPWT significantly reduced the levels of IL-6 and TNF-α , decreased the levels of phospho-Serine 307 and phospho-JNK, increased the level of phospho-tyrosine of IRS-1, and further reduced insulin resistance at 3 and 10 days after the radical debridement in diabetic patients with deep foot infection.The deep foot infections of all the diabetic patients were controlled 10 days afterwards with NPWT.Conclusion: NPWT can be safely applied in acutely debrided DDFI.Negative pressure wound therapy using vacuum-assisted closure reduces insulin resistance in diabetic patients with deep foot infection.insulin resistance seems to be the useful parameter for both diagnosis and monitoring of treatment of DDFI.