Objective To investigate the structural and functional changes of immune system in aging Sprague-Dawley rats. Methods Sixty SPF 4 -6-week old SD rats (male∶ female =1∶ 1) were used in this study. Ten of them were randomly taken and euthanized every 6 months. The dynamic changes of T cell proliferation, expression of cytokines, serum levels of SOD and MDA and histopathology were examined. Results Obvious histological changes of thymus and spleen were observed in the aging rats. Compared with the young SD rats, in the aging rats, the lymphocyte transformation ability was decreased ( P <0.05, P <0.01), number of splenic cells was declined ( P <0.05, P <0.01), NK ( P <0.05, P <0.01) and T cell subset was reduced ( P <0.05, P <0.01), and the production of IL-2 was decreased as well ( P <0.05, P <0.01). The serum level of SOD in old rats was lower, MDA was increased, with significant differences ( P <0.05, P <0.01). The immunohistochemical staining showed that more extensive staining was found in the nuclei of thymocytes from the aging rats, while the 8?OHdG formation in thymic tissues was mostly located in the thymic medulla. Conclusions Aging process is accompanied by immune impairment, oxidative stress can also impair the immune response in aging rats. Our findings indicate that structural and functional alterations of immune system in aging rats may be closely related with oxidative damages.