Purpose: Investigation of the dose–time–effect dependency of the behavior of mice and rats after irradiation with accelerated protons and comparison of these data with the morphological changes in the hippocampus and the cerebellum of rodents. Material and methods: Experiments were performed on outbred adult female ICR mice (CD-1), SPF categories, body weight 30–35 g, of the age of 10 weeks – total number 61 animals, and on 39 male Sprague Dawley outbred rats weighing 190–230 g, aged 6.5–7.5 weeks. The animals were irradiated with accelerated protons with energy of 70 MeV on the medical beam of the phasotron of the Joint Institute for Nuclear Research (Dubna). Mice were placed in individual containers and irradiated 4 ones at a time. Irradiation was performed in a modified Bragg peak at doses of 0.5; 1; 2.5 and 5 Gy in caudocranial and craniocaudal direction. Rats were divided into 2 groups: intact control and group irradiated with 170 MeV protons at a dose of 1 Gy, dose rate of 1 Gy / min in the craniocaudal direction. The behavioral responses of experimental animals were tested in the Open Field test on days 1, 7, 14, 30, 90 in rats and on days 8, 30, and 90 in mice. Quantitative analysis of the dilution of Purkinje cells in the rat cerebellum was made, as well as morphological changes in the rat hippocampal neurons. It was shown a development of structural changes after irradiation with protons in neurons of different severity at different times after exposure: after 30 and 90 days. Results: In the period of 1–8 days after proton irradiation of mice and rats in non-lethal doses (0.5–5.0 Gy), there is a dose-independent decrease in the main indicators of the spontaneous locomotor activity of rodents. By the 90th day after irradiation, there is a clear tendency to normalize the indicators of OIR in all groups of irradiated animals, while the ES remains elevated. Disruption of motor activity of rodents irradiated with protons in the early period and its relative normalization in the late post-irradiation period occur on the background of an increased number of morphologically altered and dystrophic neurons in the hippocampus and rarefied of Purkinje cells in the cerebellum. Conclusion: The complex hierarchical structure of the central nervous system, the dependence of its function on the state of the whole organism and its hormonal background, as well as on the state of the blood supply and other factors, along with its high plasticity, require complex physiological, morphological and neurochemical approaches in analyzing the radiobiological effect of corpuscular radiation, taking into consideration the unevenness in dose distribution during irradiation.