Objective: One of the possible protective factors that can protect target vascular cells (endothelial, smooth muscle cells) from damage during the development of metabolic syndrome (MetS) is hydrogen sulfide (H2S). Design and method: A study was carried out in male Wistar rats weighing 250–320 g, 140 days old at the end of research. The rats from the control group were fed standard rat chow. The rats from the experimental group had a high-fat high-carbohydrate (HFHC) diet. Biochemical parameters of rat blood were determined. The concentration of H2S in the blood serum and adipose tissue of rats was determined by the photometric method at 670 nm. The expression of the H2S synthesis enzyme CSE was studied in aortic tissue samples using Western blot. Results: It was found that HFHC diet led to an increase in body weight, obesity, hyperglycemia, insulin resistance, dyslipidemia, and leptinemia in the experimental group rats. It was found that the concentration of H2S significantly decreased in the blood serum and adipose tissue of rats with MetS. The rate of production of H2S in adipose tissue of rats with MetS also decreased. In the aortic tissue of rats with MetS, there was a decrease in the amount of protein of the CSE. Conclusions: Changes in the activity of the H2S/CSE system in MetS may be additional evidence of the development of vascular dysfunction in metabolic disorders.