Nitrite is actively being considered and evaluated as a source of nitric oxide (NO) for both topical and systemic clinical applications. A major limitation for the many promising applications of nitrite based therapy is that the dosing and duration of action are difficult to control. We have developed a nanoparticle delivery platform that utilizes a novel solid phase thermal reduction process to convert nitrite to either NO or N 2 O 3 within the nanoparticle [1]. NO is released in a slow sustained manner when the dry nanoparticles are exposed to moisture. Release rates and NO content are easily tuned with this platform. The NO releasing nanoparticles (NOnps) have been tested in vivo for both topical and systemic applications. Topically NOnps are highly effective as a broad spectrum antimicrobial agent that also enhances wound healing [2,3]. The nanoparticles can deliver NO transdermally as is evident from their efficacy as a topical therapy for erectile dysfunction [4] and for MRSA infected abscesses. Most recently, it has been demonstrated in a hamster skin flap model that topically administered NOnps induce increased tissue perfusion in the full thickness of the skin below the administered NOnps. Systemically administered NOnps have an extended circulation time with a prolonged physiological response consistent with sustained NO release [5–7]. The NOnps are anti-inflammatory and vasodilatory. They have been shown to minimize HBOC toxicity and short circuit the proinflammatory cascade associated with hemorrhagic shock. Together these preclinical results indicate that this platform can harness the considerable therapeutic potential of nitrite for both topical and systemic applications.Nothing to disclose.