Oxidative　stress　is　a　major　cause　of　skin　injury　induced　by　damaging　stimuli　such　as　UV　radiation.　Currently,　owing　to　their　immunomodulatory　properties,　mesenchymal　stem　cell-derived　exosomes　(MSC-Exo),　as　a　nanotherapeutic　agent,　have　attracted　considerable　attention.　Here,　we　investigated　the　therapeutic　effects　of　MSC-Exo　on　oxidative　injury　in　H2O2-stimulated　epidermal　keratinocytes　and　UV-irradiated　wild　type　and　nuclear　factor-erythroid　2-related　factor-2　(Nrf2)　knocked　down　cell　and　animal　models.　Our　findings　showed　that　MSC-Exo　treatment　reduced　reactive　oxygen　species　generation,　DNA　damage,　aberrant　calcium　signaling,　and　mitochondrial　changes　in　H2O2-stimulated　keratinocytes　or　UV-irradiated　mice　skin.　Exosome　therapy　also　improved　antioxidant　capacities　shown　by　increased　ferric　ion　reducing　antioxidant　power　and　glutathione　peroxidase　or　superoxide　dismutase　activities　in　oxidative　stress-induced　cell　and　skin　injury.　In　addition,　it　alleviated　cellular　and　histological　responses　to　inflammation　and　oxidation　in　cell　or　animal　models.　Furthermore,　the　NRF2　signaling　pathway　was　involved　in　the　antioxidation　activity　of　MSC-Exo,　while　Nrf2　knockdown　attenuated　the　antioxidant　capacities　of　MSC-Exo　in　vitro　and　in　vivo,　suggesting　that　these　effects　are　partially　mediated　by　the　NRF2　signaling　pathway.　These　results　indicate　that　MSC-Exo　can　repair　oxidative　stress-induced　skin　injury　via　adaptive　regulation　of　the　NRF2　defense　system.　Thus,　MSC-Exo　may　be　used　as　a　potential　dermatological　nanotherapeutic　agent　for　treating　oxidative　stress-induced　skin　diseases　or　disorders.　©　2020　Elsevier　Ltd