Background:　A　diverse　group　of　physiologically　active　peptides/proteins　are　present　in　the　salivary　glands　of　horsefly　Tabanus　yao　(Diptera,　Tabanidae)　that　facilitate　acquisition　of　blood　meal.　However,　their　roles　in　the　regulation　of　local　inflammation　remains　poorly　understood.　Methods:　Induction　expression　profiles　of　immune-related　molecules　in　the　salivary　glands　of　T.　yao　was　analyzed　by　quantitative　PCR　(qPCR)　after　bacterial　feeding.　A　significantly　up-regulated　molecule　(cecropin-TY1)　was　selected　for　anti-inflammatory　assay　in　lipopolysaccharide　(LPS)-stimulated　mouse　peritoneal　macrophages.　The　transcription　levels　of　inducible　NO　synthase　(iNOS)　and　pro-inflammatory　cytokines　were　quantified　by　qPCR.　Nitric　oxide　(NO)　production　was　determined　by　Griess　reagent.　Pro-inflammatory　cytokine　production　was　determined　by　an　enzyme-linked　immunosorbent　assay　(ELISA).　The　inflammatory　signals　were　assayed　by　Western　blotting　analysis.　The　secondary　structure　of　cecropin-TY1　was　measured　by　Circular　dichroism　(CD)　spectroscopy.　Interaction　of　cecropin-TY1　with　LPS　was　evaluated　by　the　dissociation　of　fluorescein　isothiocyanate　(FITC)-conjugated　LPS　aggregates　and　neutralization　of　LPS　determined　by　a　quantitative　Chromogenic　End-point　Tachypleus　amebocyte　lysate　(TAL)　assay　kit.　Homology　modeled　structure　analysis　and　mutation　of　key　residues/structures　were　performed　to　understand　its　structure-activity　relationship.　Results:　Cecropin-TY1　was　demonstrated　to　possess　high　anti-inflammatory　activity　and　low　cytotoxicity　toward　mouse　macrophages.　In　LPS-stimulated　mouse　peritoneal　macrophage,　addition　of　cecropin-TY1　significantly　inhibited　the　production　of　nitric　oxide　(NO)　and　pro-inflammatory　cytokines.　Further　study　revealed　that　cecropin-TY1　inhibited　inflammatory　cytokine　production　by　blocking　activation　of　mitogen-activated　protein　kinases　(MAPKs)　and　transcriptional　nuclear　factor-kappa　B　(NF-kappa　B)　signals.　Cecropin-TY1　even　interacted　with　LPS　and　neutralized　LPS.　The　secondary　structure　analysis　revealed　that　cecropin-TY1　adopted　unordered　structures　in　hydrophobic　environment　but　converted　to　a-helical　confirmation　in　membrane　mimetic　environments.　Homology　modeled　structure　analysis　demonstrated　that　cecropin-TY1　adopted　two　alpha-helices　(Leu3-Thr24,　Ile27-Leu38)　linked　by　a　hinge　(Leu25-Pro26)　and　the　structure　surface　was　partly　positively　charged.　Structure-activity　relationship　analysis　indicated　that　several　key　residues/structures　are　crucial　for　its　anti-inflammatory　activity　including　a-helices,　aromatic　residue　Trp2,　positively　charged　residues　Lys　and　Arg,　hinge　residue　Pro26　and　N-terminal　amidation.　Conclusions:　We　found　a　novel　anti-inflammatory　function　of　horsefly-derived　cecropin-TY1　peptide,　laying　groundwork　for　better　understanding　the　ectoparasite-host　interaction　of　horsefly　with　host　and　highlighting　its　potency　in　anti-inflammatory　therapy　for　sepsis　and　endotoxin　shock　caused　by　Gram-negative　bacterial　infections.