The effect of immersion hypothermia (IН) on proteolysis activity in adult male rats, which was performed at 0 °C for 5 min in the “forced swimming” test, studied; the body temperature decreased to 27.5 ± 0.5°C. In blood serum and non-nuclear fractions of homogenates of cerebral cortex, hypothalamus, cerebellum, brainstem, lungs, heart, liver and kidneys tissues were determined the total proteinase activity (TPA), non-trypsin-like proteinases (NTPs), such as chymase, prostate-specific antigen, partially tonin, kallikrein rK9, as well as trypsin-inhibitory activity of α-1-proteinase inhibitor (α-1-PI), α-2-macroglobulin (α-2-MG) by highly sensitive (10-9–10-10 g) enzymatic methods. It is noted that IH led to the TPA increase in all studied tissues (4-84 times), which corresponds to the psycho-emotional effects and the phenomenon of hormesis. After 24 h, TPA decreased, remaining above the control level, and in the kidneys increased further (90 times). NTLP activity as a result of IH increased in blood serum and cerebellum, decreased in the hypothalamus, and after 24 h increased further in serum (7 times), cerebellum, and heart. The activity of α-1-PI also increased in the brainstem, lungs, heart and kidneys, and decreased after 24 h in serum below the control level, and in the brainstem remained high, protecting against proteolytic attack. The activity of α-2-MG increased in the hypothalamus, heart, and cerebral cortex, maximum in the brainstem (2-5 times), and after 24 h - more significantly (24 times), but there were no changes in the cerebellum, where its initial level is the biggest. Thus, the development of IG as a result of swimming in cold water for 5 min at 0oC has a stimulating effect on the body and leads to a significant activation of the reactions of limited proteolysis.