Psoriasis　is　a　common　chronic　inflammatory　skin　disease　that　significantly　affects　patients＇quality　of　life.　There　is　no　cure　for　psoriasis,　and　available　treatments　are　not　completely　effective.　We　have　previously　found　that　hydroxytyrosol　(HT)　has　anti-psoriatic　effects　in　vitro.　In　the　present　study,　we　aimed　to　investigate　the　therapeutic　effects　of　HT　on　psoriasis　in　vivo　and　to　explore　the　underlying　mechanisms.　We　explored　the　effects　and　molecular　mechanisms　of　HT　on　imiquimod　(IMQ)-induced　psoriasis-like　dermatitis　in　mice　and　an　M5-induced　in　vitro　cell　model　using　real-time　PCR,　western　blotting,　hematoxylin-eosin　staining,　immunohistochemistry,　and　enzyme-linked　immunosorbent　assay.　HT　(10　mg/kg/d　or　50　mg/kg/d,　by　gavage)　ameliorated　IMQ-induced　clinical　manifestations　in　mice.　Moreover,　HT　ameliorated　the　histopathological　changes　and　decreased　the　spleen　index　and　levels　of　pro-inflammatory　cytokines,　such　as　interleukin　(IL)-17　A,　IL-23,　and　IL-22,　in　mouse　serum　or　skin.　Mechanistically,　HT　application　inhibited　the　activation　of　ERK　and　NF-&　kcy;B　signaling　in　the　skin　samples.　Consistently,　in　vitro　analysis　showed　that　HT　significantly　inhibited　inflammation　via　ERK　and　NF-kappa　B　signaling　in　a　cellular　model　of　psoriasis.　Our　results　indicate　that　HT　alleviates　IMQ-induced　psoriasis-like　dermatitis　by　inhibiting　the　ERK　and　NF-kappa　B　signaling　pathways,　suggesting　that　HT　has　a　promising　therapeutic　application　in　psoriasis　treatment.