Oxidative　stress　injury　is　an　important　link　in　the　pathogenesis　of　diabetes,　and　reducing　oxidative　stress　damage　caused　by　long-term　hyperglycemia　is　an　important　diabetic　treatment　strategy.　Melatonin　has　been　proved　to　be　a　free　radical　scavenger　with　strong　antioxidant　activity,　and　its　protective　effect　on　diabetes　and　the　complications　has　been　confirmed.　However,　the　role　and　potential　mechanism　of　melatonin　in　oxidative　stress　injury　of　diabetic　aorta　have　not　been　reported.　Besides,　Notch　signaling　pathway　plays　an　important　role　in　vascular　growth,　differentiation,　and　apoptosis.　We　speculated　that　melatonin　could　improve　oxidative　stress　injury　of　diabetic　aorta　through　Notch1/Hes1　signaling　pathway.　STZ-induced　diabetic　rats　and　vascular　smooth　muscle　cells　(VSMCs)　cultured　with　high　glucose　were　treated　with　or　without　melatonin,　melatonin　receptor　antagonist　Luzindole,　gamma-secretase　inhibitor　DAPT　respectively.　We　found　that　melatonin　could　improve　the　oxidative　stress　injury　of　diabetic　aorta　and　reduce　the　apoptosis　of　VSMCs.　Interestingly,　melatonin　could　activate　Notch1　signaling　pathway,　play　an　antioxidant　role,　and　reduce　the　expression　of　apoptosis-related　proteins.　However,　these　protective　effects　could　be　largely　eliminated　by　Luzindole　or　DAPT.　We　concluded　that　the　repression　of　Notch1　signaling　pathway　would　inhibit　the　repair　of　oxidative　stress　injury　in　diabetes.　Melatonin　could　ameliorate　oxidative　stress　injury　and　apoptosis　of　diabetic　aorta　by　activating　Notch1/Hes1　signaling　pathway.