Introduction: Although radiotherapy based on X-ray improves the survival of patients suffering brain tumours, it also leads to deleterious effects on the inflammatory system such as lymphopenia, which in turn decreases the immunotherapeutic response and is associated to a poor prognosis. Proton therapy has recently emerged as a new radiation strategy for brain tumours. Thanks to its precise dose deposition, it enables to spare healthy tissue. Moreover, due to its different biological effects on the irradiated tissue, it could results in less harmful effects for systemic inflammation. In this project, we aim to evaluate if brain radiation with proton therapy is less deleterious for circulating leukocytes than conventional brain radiotherapy as a function of other variables. Materials & Methods: Tumour-free mice were irradiated twice a day (2.5 Gy/session) for four consecutive days for a total dose of 20Gy with X-rays (X-rad 225 Cx GIP CYCERON, Caen) or protons beam (25MeV PRECy platform, Strasbourg). Groups of mice were defined according to spatial coverage (whole-brain or hemisphere) and dose rate (1 or 2Gy/min). Blood samples were collected before, during and after radiation and circulating leukocytes populations and cytokines were analyzed by flow cytometry. Results: Mice weight decreased after whole-brain radiation with X-rays but not with protons beam. Blood sampling confirmed radiation-induced profound decrease in leukocytes early after irradiation with X-rays, especially for CD3+ lymphocytes and the CD4+ lymphocytes subpopulation. Results seem to show an opposite effect in CD45+ CD11b+ myeloid cells. Interestingly, we noticed that whole-brain irradiation induced a more pronounced effect than hemispheric irradiation. Changes in leukocytes after proton irradiation suggest a conservative effect on circulating lymphocytes. Conclusion: Proton therapy appears as a better radiotherapy strategy for brain tumours to spare circulating leukocytes. The mechanisms behind these observations are under investigation.