Abstract: Topical exposure of nitric oxide gas to wounds such as chronic non-healing wounds may be beneficial in promoting healing of the wound and in preparing the wound bed for further treatment and recovery. Nitric oxide gas may be used, for example, to reduce the microbial infection and burden on these wounds, manage exudate secretion by reducing inflammation, upregulate expression of endogenous collagenase to locally debride the wound, and regulate the formation of collagen. High concentration of nitric oxide ranging from about 160 to 400 ppm may be used without inducing toxicity in the healthy cells around a wound site. Additionally, exposure to the high concentration for a first treatment period reduces the microbial burden and inflammation at the wound site and increase collagenase expression to debride necrotic tissue at the wound site.