Depression　is　a　disturbing　psychiatric　disease　with　unsatisfied　therapy.　Not　all　patients　are　sensitive　to　anti-depressants　currently　in　use,　side-effects　are　unavoidable　during　therapy,　and　the　cases　with　effectiveness　are　always　accompanied　with　delayed　onset　of　clinical　efficacy.　Delivering　brain-derived　neurotrophic　factor　(BDNF)　to　brain　seems　to　be　a　promising　therapy.　However,　a　better　approach　to　delivery　is　still　rudimentary.　The　purpose　of　our　present　work　is　to　look　for　a　rapid-onset　and　long-lasting　therapeutic　strategy　for　major　depressive　disorder　(MDD)　by　effectively　delivering　BDNF　to　brain.　BDNF,　fused　with　cell-penetrating　peptides　(TAT　and　HA2),　was　packaged　in　adenovirus　associated　virus　(AAV)　to　construct　the　BDNF-HA2TAT/AAV　for　intranasally　delivering　BDNF　to　central　nervous　system　(CNS)　via　nose-brain　pathway.　Intranasal　administration　of　BDNF-HA2TAT/AAV　to　normal　mice　displayed　anti-depression　effect　in　forced　swimming　test　when　the　delivery　lasted　relatively　longer.　The　AAV　applied　to　mice　subjected　to　chronic　mild　stress　(CMS)　through　intranasal　administration　for　10　days　also　alleviated　depression-like　behaviors.　Western-blotting　analysis　revealed　that　BDNF-HA2TAT/AAV　nasal　administration　enhanced　hippocampal　BDNF　content.　These　results　indicate　intranasal　administration　of　constructed　BDNF-HA2TAT/AAV　exerts　anti-depression　effect　in　CMS　mice　by　increasing　hippocampal　BDNF,　suggesting　that　this　strategy　holds　a　promising　therapeutic　potential　for　MDD.