Ｏｂｊｅｃｔｉｖｅ　To investigate the protective effects of protein transduction domain 4-Cu, Zn superoxide dismutase fusion protein (PTD4-Cu, Zn-SOD) against cerebral ischemia/reperfusion injury (CI/RI) in rats.　Methods　A total of 120 adult male rats were randomly divided into four groups (n=30): sham group (group SH), ischemia/reperfusion group(group I/R), superoxide dismutase group (group SOD), PTD4-Cu, Zn-SOD group (group PTD4-SOD). For group I/R, SH and PTD4-SOD, their bilateral carotid arteries were temporarily occluded over 6 min after electrocoagulation of bilateral vertebral arteries for 24 h to establish a CI/RI model. Before reperfusion, rats in group SOD and PTD4-SOD were injected with 6 mg/kg SOD or 6 mg/kg PTD4-SOD via the tail vein, respectively, while those in group SH and group I/R received the same volume of phosphate buffer saline(PBS) via the tail vein. Then the brain tissue samples were harvested 2, 6, 12, 24, 72 h after reperfusion(n=6). The pathological changes of the hippocampus were observed by hematoxylin-eosin (H-E) staining. The activity of SOD in the hippocampus was detected by xanthine oxidase method. The apoptosis rate of hippocampal cells was examined by flow cytomrtry.　Results　H-E stain: the neurons in hippocampal CA1 region of group SH were tightly arranged, where the cytoplasm was reddish and the nuclear was stained blue, with the clear nucleus. The neurons of group I/R were arranged in a disordered manner and idioblast counts were increased. The cytoplasm and nucleolus obviously shrunk, where the nucleolus disappeared or dissolved. Compared with group I/R, group PTD4-SOD presented tightly arranged neurons in hippocampal CA1 region, with little sparse idioblasts. The changes in group SOD was between group PTD4-SOD and group I/R. SOD activity test: compare with group SH, remarkable difference was found in groups I/R, SOD and PTD4-SPD 12, 24 and 72 h after perfusion (P<0.05). Compared with group PTD4-SOD, remarkable difference were found in group I/R and group SOD at each time point (P<0.05). The cell apoptosis rate of hippocampus: compared with group SH, there were marked differences in the apoptosis rate in group I/R, group SOD, group PTD4-SOD at each time point (P<0.05). Compared with group PTD4-SOD, remarkable difference were found in group I/R and group SOD at each time point (P<0.05).　Conclusions　PTD4-Cu, Zn-SOD can relieve CI/RI, which may be associated with enhanced SOD activity and free radical scavenging.