Aims:　The　intracellular　superoxide　anion　has　been　shown　to　be　involved　in　brain　injury.　TAT-Superoxide　dismutase　(TAT-SOD)　can　be　transduced　across　the　cell　membrane　to　scavenge　superoxide.　This　protein＇s　unique　properties　make　it　a　promising　therapeutic　candidate　to　attenuate　cerebral　damage.　In　this　study,　we　sought　further　the　understanding　of　the　fusion　protein＇s　cerebral　protective　effects　and　the　mechanism　which　is　exerted　in　these　effects.　Main　methods:　Male　Sprague　Dawley　rats　(n　=　100,　230　+/-　20　g)　were　divided　randomly　into　five　experimental　groups:　a　sham　group,　a　cerebral　Ischemia/Reperfusion　(I/R)　group　treated　with　saline　(20　ml/Kg,　i.p.),　and　three　cerebral　I/R　groups　treated　with　TAT-SOD　(25　KU/ml/Kg,　i.p.)　at　either　2　h　before　I/R,　2　h　after　I/R　or　4　h　after　I/R.　Cerebral　I/R　injury　was　facilitated　by　inducing　ischemia　for　two　hours　followed　by　24　h　reperfusion.　The　levels　of　SOD,　Malondialdehyde　(MDA),　and　ATPase　in　cerebral　tissues　were　determined.　The　apoptotic　indexes　were　evaluated,　and　apoptosis　genes　were　analyzed　immunohistochemically.　Key　findings:　TAT-SOD　treatment　significantly　increased　cerebral　SOD　and　ATPase　activities,　decreased　MDA　content,　and　remarkably　reduced　apoptosis　indexes.　TAT-SOD　treatments　2　h　before　or　after　I/R　significantly　reduced　caspase-3　and　bax　proteins　and　boosted　bcl-2　protein,　while　the　treatment　at　4　h　after　I/R　showed　no　influence　on　the　three　proteins.　Significance:　TAT-SOD　treatment　effectively　enhanced　cerebral　antioxidant　ability,　reduced　lipid　peroxidation,　preserved　mitochondrial　ATPase　and　thus　inhibited　nerve　cell　apoptosis.　The　effective　treatment　window　extended　from　2　h　before　to　2　h　after　I/R.　(C)　2011　Elsevier　Inc.　All　rights　reserved.