Given the widespread use in medicine of opioid analgesics, today it is extremely important to study the morphofunctional changes of various organs with prolonged exposure to opioids. In the modern scientific literature there are works in which changes of biochemical indicators of blood at use of narcotic analgesics in experiment are covered. To study the changes in the biochemical parameters of blood and urine with long-term use of Nalbuphine is an important area of research. The aim of the study was to detect changes in some biochemical parameters of blood and urine of rats at six-week administration of therapeutic doses of Nalbuphine. The study was based on 40 white adult male rats weighing 180-260 g, which were injected daily for six weeks with Nalbuphine injection 20 mg daily, intramuscularly in therapeutic doses. Daily diuresis and creatinine content were determined in urine samples. The content of total protein, creatinine, urea, calcium and phosphorus was determined in blood samples. The glomerular filtration rate was also determined by the clearance of endogenous creatinine. All statistical calculations were performed using R Studio v.1.1.442 and R Commander v.2.4-4 software. The results of the study showed that six weeks of therapeutic doses of Nalbuphine affects the filtration and reabsorption function of the kidney. The use of Nalbuphine for two weeks does not cause significant changes in biochemical parameters, but the established deviations may indicate the first signs of renal dysfunction. Further use of Nalbuphine, including the end of the sixth week of the experiment, leads to significant changes in the filtration and reabsorption functions of the kidneys, as evidenced by statistically significant changes in the biochemical parameters of blood and urine of rats. The data of the study can be used to compare with changes in the functional state of the kidneys caused by prolonged use of Nalbuphine, its withdrawal and the use of other drugs in combination with Nalbuphine. It is also advisable to compare the results of the study with the morphological changes of the kidneys at different times of use of Nalbuphine.