An experimental approach was developed to quantify the influence of α and γ radiolysis of water on the dissolution kinetics of the spent UO2 fuel matrix. Two types of experiments were carried out: leaching experiments in deaerated media with UO2 fuel pellets doped with alpha emitters (238Pu), and leaching experiments with UO2 fuel pellets (standard or doped with alpha emitters) submitted to γ irradiation. Leaching experiments on UO2 pellets doped with alpha-emitters in deionized water and in deaerated media showed a correlation between the alpha particle flux at the reaction interface and uranium release in solution. The higher the alpha particle flux at the reaction interface, the higher the uranium release rate (mean rates over 30 days at S/V = 3 m−1: 15-year batch, r = 2.5 mg·m−2d−1; 1500-year batch, r = 0.2 mg·m−2d−1; 40 000-year batch, r = 0.04 mg·m−2d−1). These results, obtained at low flux levels that are realistic on a disposal time scale, supplement existing data describing the effect of doping on UO2 alteration at higher flux levels. Leaching experiments with the 1500-year batch under gamma irradiation allowed us to quantify the impact of a gamma irradiation field on the UO2 release. At 650 Gy·h−1 the effects of alpha irradiation appear to be fully masked since the uranium release is 450 times higher than in the presence of the alpha irradiation field alone. The Chemsimul code was also used to model water radiolysis and uranium release into solution.