Objective: The aim of this study was to explore the clinical effects of intralesional administration of an epidermal growth factor (EGF) up to complete wound closure. Methods: Seventeen diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution were enrolled in the study. Mean ulcer size was 15.5 +/- 7.5 cm(2). Intralesional injections of 75 mu g of Heberprot-P three times per week for 5-8 weeks were given up to complete wound healing. Results: Full granulation response was achieved in all patients in 32.4 +/- 6.6 days. Complete wound closure was obtained in 16 (94.1%) cases in 53.1 +/- 4.7 days. The most frequent adverse events were burning sensation, tremors, chills and pain at the site of administration. After 1-year follow-up, only one patient relapsed. Conclusions: Intralesional EGF administration up to complete closure can be safe, effective and suitable to improve healing of chronic diabetic foot ulcer (DFU).