Use of narcotic drugs in clinical practice for the purpose of obtaining analgesic and anti-inflammatory effects requires a comprehensive morphological study of the peculiarities of structural arrangement of organs under the conditions of exposure to opioids. The aim of our study was to establish the peculiarities of restructuring of the structural components of the pancreas under the conditions of long-time exposure to opioids in the experiment. The study included 24 adult laboratory white male rats. The test animals were divided into 2 groups, the experimental and control ones. The experimental animals were daily administered narcotic analgesic nalbuphine intramuscularly (once a day in the same interval) for four weeks, and the control animals were administered saline solution. The following research methods were used: bloodstream injection followed by translucence of sections of the pancreas and their photographing, morphometry of the vessels of the pancreatic hemomicrocirculatory bed, histological, histochemical studies and electron microscopy of the pancreas, blood biochemistry test; statistical processing of the study results using a software package. After four weeks of opioid exposure, lesion of the pancreatic parenchyma microstructure was observed, manifested by swelling and infiltration by lymphocytes and macrophages of the pancreatic connective tissue stroma, disorganization of the exo- and endocrine parts of the parenchyma, deep destructive changes in the excretory ducts, as well as in the vessels of the hemo- and lympho-microcirculatory bed of the pancreas. At the ultrastructural level, deep dystrophic changes of exo- and endocrinocytes of the pancreas were identified, in particular, loss of regular shape, karyopyknosis and karyorrhexis of the nuclei, swelling and clearing of cytoplasm, development of microcystic degeneration of cells, loosening and disorganization of the basement membrane, which can result in impairment of exocrine function of the pancreas and complication of the process of secretory granules excretion into the lumen of the intercalated ducts. A significant decrease, compared to the control group, in the diameter of arterioles, density of exchange vessels network, as well as increase in the diameter of venules, the indicator of trophic activity of the tissue, are the evidence of destructive changes in the hemomicrocirculatory bed of the pancreas under the effects of nalbuphine. Significant changes in blood biochemistry parameters (alanine aminotransferase, aspartate aminotransferase) after a four-week administration of nalbuphine are illustrative of the process of pancreatic tissue destruction. Therefore, four-week administration of opioid leads to profound changes in the micro- and ultrastructure of the pancreas, vessels of its hemomicrocirculatory bed, and blood biochemistry parameters in experimental white rats.