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Background. One of the significant factors in the progression of fibrotic changes in the liver is hepatocyte steatosis, that persists in drug addicted patients even after the elimination of the hepatitis C virus and cessation of drug use. Analysis of the pathomorphogenesis of hepatic steatosis in opioid dependence (OZ) will make it possible to assess the factors that affect ultrastructural changes in hepatocytes and the processes of lipid granule (LH) degradation. Objective. Assessment of ultrastructural changes in LH in the liver tissue of patients with OZ. Material and methods. Histological preparations of liver tissue from 20 patients with OZ aged 21 to 40 years (18 men and 2 women) with different duration of OZ and opioid tolerance. Results. There was established the following dependence of ultrastructural changes in the liver in patients with different duration of OZ and opioid tolerance. The most pronounced changes were noted in the group of patients with prolonged (more than 6 years) opioid intoxication and high tolerance to opioids in the liver tissue, in whom, along with severe steatosis, there were more significant violations of the mechanisms of LH degradation, destruction of cristae in mitochondria, a decrease in the number of lipophagosomes and PH with signs of superficial degradation than in the group of patients with OZ duration up to 6 years, as well as with moderate and high opioid tolerance. Conclusions. Ultrastructural changes in hepatocytes in the form of progression of steatosis in the centrilobular and periportal zones, a decrease in the activity of LH degradation, gross morphological changes in mitochondria, a decrease in the activity of surface LH degradation depend on the activity and duration of opioid dependence and are more pronounced with long-term (more than 6 years) highly progressive opioid dependence.