Thirty five adult male albino rats were used in this study. They were divided into 7 groups: Group I (Control), Group II (low dose Zno NPs group) , Group III (medium dose Zno NPs group) , Group IV (high dose Zno NPs group), Group V (low dose Zno NPs-selenite group), Group VI (medium dose Zno NPs-selenite group), Group VII (high dose Zno NPs-selenite group): tissue of the spleen was examined histopathologically and immunohistochemical , Determination of blood cells count (number of white blood cells (WBCs), red blood corpuscles (RBCs) and platelets. Also tissue level of Hydrogen peroxide (H2O2) and paraoxonase-1(pon-1): for detection of oxidative stress estimated for all groups, PCR detection of apoptosis inducing factor (AIF), apoptotic protease activating factor-1 and caspases 3 and Zinc level in the spleen. Results of the present study showed that, compared to controls: orally intake of Zinc oxide nanoparticles (Zno NPs) cause marked changes in spleen tissues as thickening of capsule, thickening of trabeculae , destruction of white pulp and red pulp expansion especially in groups receiving zinc oxide nanoparticles only and these changes markedly decreased on groups receiving selenium as protection