Background: Development of pharmacotherapy with the use of opiates and opioids requires elaboration of measures to prevent and offset the side effects and complications that they cause, especially for the brain sensitive to the drug therapy effects because of the nature of its structure and function. Material and methods: The study was carried out on 24 mature white male rats aged 4.5 – 5.5 months and body weight 130-180 g. Nalbufin was intramuscularly injected to the experimental animals as follows: 1st week – 8mg/kg, 2nd week – 15 mg/kg, 3rd week – 20 mg/kg, 4th week – 25 mg/kg, 5th week – 30 mg/kg, 6th week – 35 mg/kg. The work was carried out using the method of electron microscopy. The study and photographing of the material was conducted with the aid of УЕМБ-100 К microscope at acceleration speed 75 kV and magnification on the microscope screen ´ 4000– 8000. Results: The work presents data on ultrastructural organization of the corpus callosum of the white rat in the norm and in the dynamics of the long-term effect of opioid. Corpus callosum of the white rat is formed by myelinated and nonmyelinated fibers. The first changes in the ultrastructure of corpus callosum are observed already after 2 weeks of injecting nalbufin to the experimental animals and continue to increase throughout the subsequent stages of the experiment. Principal manifestation of the neuropathy of the corpus callosum, in case of injection of nalbufin, during 6 weeks is degradation of axis cylinders of the nerve fibers, glial cells. Morphological changes characteristic of microangiopathy are taking place in parts of the hemomicrocirculatory bloodstream of corpus callosum. Conclusions: Thus, continuous injection of nalbufin predetermines changes in ultrastructural organization of the corpus callosum. This work is the basis for further studies to be conducted by morphologists and neurologists with the objective of elaboration in the future of the new methods of diagnosing and prevention of brain pathology caused by prolonged use of opioids.