Abstract Introduction: Post- traumatic stress disorder (PTSD) is a psychiatric disorder which occurs after the experience of life threatening events as natural disasters, military combat, serious accidents, or violent sexual assaults. It has a severe impact on quality of life. Aim of the work to study the effect of single prolonged stress on the structure of hippocampus in adult male albino rats. Materials and Methods 20 adult male albino rats were randomly divided into four groups control group (group I) and single prolonged stress group examined at day 1(group II), day 7 (group III) and day 14 (groupIV). Rats were restrained by placing them in plastic restrainers, immediately followed by 20 minutes of forced swimming in 20–24°C water. Rats were exposed to ether until general anesthesia then they were placed in their home cages. At the end of the experiment, the hippocampi were taken and processed for light microscopic study. Results pyramidal cells of the CA3 region of the hippocampus showed progressive degeneration with passage of time from day 1 to day 14 with decrease in thickness. Transient increase in glial fibrillary acidic protein (GFAP) expression in the astrocytes of the hippocampus was detected at day 1 followed by reduction in GFAP expression started at day seven and continued to day 14. Conclusion post-traumatic stress PTSD causes significant structural hippocampal neuronal damage affecting the CA3 hippocampal subfield.