The present study was undertaken to evaluate the leaf extracts of Carica papaya (Linn.) on hematologic and biochemical changes occurring due to irradiation of mice to sub-lethal doses of Electron Beam Radiation (EBR).The immunomodulatory response of C. papaya (Linn.) extract to the radiological effects by determining the levels of interleukin-6. The serum total antioxidants, lipid peroxidation and the biochemical changes in liver and kidney function were assessed. Reduction in the hematological parameters like hemoglobin, RBC, WBC and platelets were seen in the irradiated groups compared to the control group. The elevated serum malondialdehyde levels indicate increased lipid peroxidation and reduced glutathione levels and total antioxidant capacity suggest prominent oxidative stress in the irradiated groups. C. papaya (Linn.) (pre-treatment + radiation) treated groups have shown significant improvements in the hematological parameters. Reduction in the malondialdehyde levels and increased reduced glutathione levels indicate amelioration of the oxidative stress. There is decrease in the cytogenetic damages in the C.papaya (Linn.) (pre-treatment + radiation) treated groups compared to the radiation control. Significant changes were seen in the interleukin-6 levels of C. papaya (Linn.) (pre-treatment + radiation) treated groups indicate enhanced immune response compared to the irradiation control groups. The results indicate that the C. papaya (Linn.) aqueous extracts play a protective role in radiation induced hematological and antioxidant suppression. Also it enhances membrane stabilization and reduces cytogenetic damages.