Aim: The study aimed to determine the structural organization and conduct a quantitative analysis of the cellular composition of rat liver sinusoids under condition of a long-term (10 weeks) experimental exposure to cannabidiol oil. Materials and Methods: An experimental study was conducted on 20 white non-linear male rats weighing 180-230 g, in compliance with ethical principles. The modeling of prolonged cannabidiol oil exposure in 14 white rats was performed through daily per os administration at a dose of 10 mg/kg/ for 10 weeks, the control group was 6 sexually mature white male rats, that oral administration the CBD carrier solvent – hemp seed oil. Histological, immunohistochemical and morphometric studies of the cellular composition of liver sinusoids were performed with statistical processing. In all comparisons, the difference was considered statistically significant at a minimum significance level of p < 0.05. Results: After 10 weeks exposure to CBD oil administration pathohistological changes in the rat liver sinusoids were not observed. There is a significant increase in the average number of Kupffer cells in the sinusoidal wall in all zones of the lobule p < 0.001, especially near the portal zone (1.58 times) compared to the control group, which can be explained by their activation in response to long-term exposure to CBD. Perisinusoidal cells in the experimental series in all areas of the liver lobule were the least compared to endothelial cells and Kupffer cells, p < 0.001. Conclusions: Histological, immunohistochemical study with quantitative analysis of the cellular composition of rat liver sinusoids indicates the safety of long-term experimental exposure to CBD oil.