OBJECTIVE: Polydeoxyribonucleotide contains a mixture of nucleotides and interacts with adenosine receptors, stimulating vascular endothelial growth factor expression and wound healing. The purpose of this study was to investigate the effect of polydeoxyribonucleotide on experimental burn wounds. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury in mice. INTERVENTIONS: Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second-degree burn. Animals were randomized to receive either polydeoxyribonucleotide (8 mg/kg/day intraperitoneally for 14 days) or its vehicle alone (0.9% NaCl solution at 100 microL/day intraperitoneally). On days 7 and 14 the animals were killed. Blood was collected for tumor necrosis factor-alpha measurement; burn areas were used for histologic and immunohistochemical examination, for the evaluation of vascular endothelial growth factor and nitric oxide synthases by Western blot, and for the determination of wound nitric oxide products. MEASUREMENTS AND MAIN RESULTS: Polydeoxyribonucleotide increased burn wound re-epithelialization and reduced the time to final wound closure. Polydeoxyribonucleotide improved healing of burn wound through increased epithelial proliferation and maturation of the extracellular matrix as confirmed by fibronectin and laminin immunostaining. Polydeoxyribonucleotide also improved neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of platelet-endothelial cell adhesion molecule-1. Furthermore, polydeoxyribonucleotide blunted serum tumor necrosis factor-alpha and enhanced inducible nitric oxide synthase and vascular endothelial growth factor expression and the wound content of nitric oxide products. CONCLUSIONS: Our study suggests that polydeoxyribonucleotide may be an effective therapeutic approach to improve clinical outcomes after thermal injury.