Context:　Gastric　ulcer　is　a　common　gastrointestinal　disorder　with　increasing　incidence　and　prevalence　attributed　to　loss　of　balance　between　aggressive　and　protective　factors.　Nobiletin　(NOB),　a　major　component　of　polymethoxyflavones　in　citrus　fruits,　has　a　broad　spectrum　of　health　beneficial　properties　including　anti-inflammatory　and　anti-tumor　activities.　Although　NOB　was　originally　shown　to　possess　anti-inflammatory　activity,　its　effects　on　gastric　ulcer　were　rarely　explored　previously.　Objective:　The　aim　of　the　present　study　was　to　investigate　the　anti-ulcerogenic　activity　of　NOB　on　ethanol-induced　gastric　ulcer　in　mice　and　to　elucidate　the　underlying　mechanisms.　Methods:　Seventy-two　male　Kunming　mice　administered　with　absolute　ethanol　(0.2ml/animal)　were　pretreated　with　NOB　(5,　10　or　20mg/kg),　cimetidine　(100mg/kg),　or　vehicles　by　intragastric　administration　in　different　experimental　groups　for　three　days,　and　animals　were　euthanized　3h　after　ethanol　ingestion.　Gross　and　microscopic　lesions,　immunological　and　biochemical　parameters　were　taken　into　consideration.　Results:　The　results　showed　that　ethanol　induced　gastric　injury,　increased　malondialdehyde　(MDA)　levels,　decreased　glutathione　(GSH)　content,　superoxide　dismutase　(SOD)　activity,　and　prostaglandin　E-2　(PGE(2))　levels,　increased　pro-inflammatory　cytokines　tumor　necrosis　factor-alpha　(TNF-)　and　interleukin-6　(IL-6)　levels　and　myeloperoxidase　(MPO)　activity,　as　well　as　the　expression　MAPK　signaling　pathway.　Pretreatment　with　NOB　significantly　attenuated　the　gastric　lesions　as　compared　to　the　ethanol　group.　Conclusions:　These　findings　suggest　that　the　gastroprotective　activity　is　attribute　to　the　improvement　of　antioxidant　activities,　the　stimulation　of　PGE(2),　and　the　reduction　of　pro-inflammatory　cytokines　through　the　MAPK　pathway.