Background: The common pathogenetic relations of type 2 diabetes mellitus (T2DM), testosterone (T) deficiency and non-alcoholic fatty liver disease (NAFLD) have indicated a new direction in the study of their mutual influence. It was found that NAFLD is more pronounced in men with T2DM and hypogonadism than in eugonadal patients and associated with hyperinsulinemia, insulin resistance, impaired lipid metabolism and adipose tissue dysfunction. However, the effects of testosterone replacement therapy (TRT) on the severity of NAFLD in men with hypogonadism have not been studied.Aims: To study the effect of TRT on the severity of NAFLD in men with T2DM and hypogonadism.MATERIALS AND METHODS: Anthropometric data, biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGTP), glucose, immunoreactive insulin, HOMA index, glycosylated hemoglobin, lipidogram), ELISA analysis (total T, LH, sex hormone binding globulin, resistin, adiponectin, leptin), as well as magnetic resonance imaging with determination of the liver fat fraction were examined.Results: The study included 60 men with T2DM and hypogonadism (mean age 54 [49; 57] years), who were randomized into 2 groups: 1 (n=30) - patients who received 1% transdermal T gel (50 mg/day) in addition to standard hypoglycemictherapy; 2 (n=30) - patients who received standard hypoglycemic therapy. The follow-up period was 6 months. T therapy was associated with a decrease in liver enzyme levels: AST by 31%, ALT by 21%, and GGTP by 15.9% (p<0.05) and the hepatic fat fraction by 1.7 times, which reflect the regress of liver inflammation, and, consequently, a decrease in the severity of NAFLD. Moreover, TRT has improved the function of adipose tissue - reduced the concentration of leptin by 1.4 times and resistin by 1.5 times, which was accompanied by an increase in adiponectin level by 1.3 times (p<0.01). The use of TRT was associated with decrease in the severity of visceral obesity, hyperinsulinemia by 1.5 times, an insulin resistance index HOMA by 2.2 times, fasting glycaemia and HbA1c levels, despite constant hypoglycemic therapy. Statistically significant decrease in the levels of total cholesterol and triglycerides was observed in men receiving TRT. Thus, a decrease in adipose tissue dysfunction and insulin resistance in men receiving TRT can be considered as a pathogenetic mechanism responsible for improving liver function and reducing the severity of NAFLD.Conclusions: TRT in men with T2DM and hypogonadism is accompanied by regress of inflammatory activity in liver and intensity of hepatocytes steatosis, reflected by decrease in liver enzymes levels and liver fat fraction.