It　is　known　that　neurotrophic　factors　are　a　major　source　of　the　neuroprotective　effects　of　olfactory　ensheathing　cells　(OECs).　However,　the　form　of　neurotrophic　factors　that　originate　from　OECs　is　not　fully　understood.　Our　previous　study　demonstrated　that　OECs　could　secrete　exosome　(OECs-Exo),　which　provided　neuroprotection　by　switching　the　phenotype　of　macrophages/microglia.　Considering　that　exosomes　could　also　be　taken　up　by　neurons,　we　explored　the　direct　effect　of　OECs-Exo　on　neuronal　survival　and　the　underlying　mechanism.　Electron　microscopy,　nano-traffic　analysis,　and　Western　blotting　were　applied　to　identify　the　OECs-Exo.　The　effect　of　OECs-Exo　on　neuronal　survival　was　tested　by　flow　cytometry　and　TUNEL　staining.　Western　blotting　and　ELISA　were　used　to　detect　neurotrophic　factors　in　purified　OECs-Exo.　We　first　isolated　OECs-Exo　and　found　that　OECs-Exo　exerted　protective　effects　on　neuronal　survival　in　response　to　TNF-alpha　challenge.　Brain-derived　neurotrophic　factor　(BDNF)　was　then　identified　in　OECs-Exo,　and　its　receptor　TrkB　in　neurons　was　activated　by　OECs-Exo　treatment.　Furthermore,　we　demonstrated　that　OECs　prevented　TNF-alpha-induced　apoptosis　in　neurons　partially　through　exosome-derived　BDNF.　Our　data　showed　that　OECs　attenuated　TNF-alpha-induced　apoptosis　in　neurons　partially　through　OEC-Exo-derived　BDNF,　which　might　provide　a　novel　strategy　for　the　neuroprotective　effect　of　OEC-Exo-based　treatment.