The present study was to evaluate the radiomitigative effect of naringenin (NRG) on the modulation of ionizing radiation (IR)‐induced spleen injury. Rats were exposed to 12 Gy (3Gy/two times/week). NRG (50mg/Kg), was orally given one hour after the first radiation dose, and daily continued during the irradiation period. Rats were sacrificed 1 day after the last dose of radiation. NRG showed a significant decrease of malondialdehyde, hydrogen peroxide with a significant elevation of superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content. Moreover, NRG confirmed the intracellular defense mechanisms through activation of nuclear factor (erythroid‐derived 2)‐like2 (Nrf2) and haem oxygenase‐1 (HO‐1) levels and their protein expression. In addition, NRG deactivated the nuclear factor‐κB (NF‐κB) and reduced the pro‐inflammatory cytokines. Further, NRG showed positive modulation in the haematological values (WBCs, RBCs, Hb, Hct% and PLt). In conclusion, these results suggested that NRG reversed the IR‐induced redox‐imbalance in the rat spleen.