Asthma　is　a　complex　disease,　characterized　by　reversible　airway　obstruction,　hyperresponsiveness　and　chronic　inflammation.　Principle　pharmacologic　treatments　for　asthma　include　bronchodilating　beta2-agonists　and　anti-inflammatory　glucocorticosteroids;　but　these　agents　do　not　target　the　main　cause　of　the　disease,　the　generation　of　pathogenic　Th2　cells.　We　previously　reported　reduction　in　allergic　inflammation　in　mice　deficient　in　the　ANP　receptor　NPRA.　Here　we　determined　whether　siRNA　for　natriuretic　peptide　receptor　A　(siNPRA)　protected　against　asthma　when　administered　transdermally.Imiquimod　cream　mixed　with　chitosan　nanoparticles　containing　either　siRNA　green　indicator　(siGLO)　or　siNPRA　was　applied　to　the　skin　of　mice.　Delivery　of　siGLO　was　confirmed　by　fluorescence　microscopy.　The　anti-inflammatory　activity　of　transdermal　siNPRA　was　tested　in　OVA-sensitized　mice　by　measuring　airway　hyperresponsiveness,　eosinophilia,　lung　histopathology　and　pro-inflammatory　cytokines.SiGLO　appearing　in　the　lung　proved　the　feasibility　of　transdermal　delivery.　In　a　mouse　asthma　model,　BALB/c　mice　treated　with　imiquimod　cream　containing　siNPRA　chitosan　nanoparticles　showed　significantly　reduced　airway　hyperresponsiveness,　eosinophilia,　lung　histopathology　and　pro-inflammatory　cytokines　IL-4　and　IL-5　in　lung　homogenates　compared　to　controls.These　results　demonstrate　that　topical　cream　containing　imiquimod　and　siNPRA　nanoparticles　exerts　an　anti-inflammatory　effect　and　may　provide　a　new　and　simple　therapy　for　asthma.