According to classical concepts, the key markers of inflammation both in the body and in the muscles are cytokines such as IL-6 and IL-10. They are able to have both pro-inflammatory and anti-inflammatory effects in muscle fiber. For example, it note that after intense physical exercise, an increase in the concentration of IL-6 mRNA in monocytes was observed and did not increase after exercise, indicating that the increase in IL-6 levels during exercise is due to activation not of immune cells, but in the skeletal muscles themselves. However, later a series of experimental studies proved that even after the restoration of the normal cytokine profile in the muscles because of severe overtraining, performance also remained at a low level. As a result, it suggested that cytokines are not a limiting factor in the development of inflammation, but are part of complex functional systems, since they can produced not only during physical activity. Therefore, a current direction in sports physiology is the study of the mechanisms of development of inflammatory reactions, as well as the search for new informative markers. In accordance with this, we conducted a literature analysis, the purpose of which is to identify and substantiate new informative markers involved in the inflammatory response in muscles. This literature review examines both the classical mechanisms of the development of the inflammatory response, based on the cytokine theory, and examines new possible elements that can play a significant role in the development of this process. For example, due to an uncontrolled increase in calcium concentration during intense physical activity, calpains activated, which can cause the destruction of protein structures in muscles. Therefore, a local inflammatory reaction may occur. This effect may significantly enhanced by NF-κB, which causes muscle disturbances by increasing the transcription of muscle-specific ubiquitin ligases, as well as regulating the expression of a number of inflammatory molecules. It should also note that NF-κB is one of the activators of inducible nitrogen synthase (iNOS) in the first stages of inflammation in muscle without the participation of macrophages. Increased production of i-NOS under conditions of disruption of physiological processes in the cell will contribute to the aggravation of oxidative stress and further cellular destabilization. The resulting overproduction of NO and large amounts of ROS within the cell may contribute to the formation of the toxic molecule peroxynitrite (ONOO-). Peroxynitrite, due to its oxidative abilities, can affect the membrane of both the cell itself and the plasma reticulum, thereby causing an additional influx of exogenous calcium and release of endogenous calcium into the cytosol, aggravating this pathological process several times.An interesting aspect to study is the role of the nervus vagus (vagus nerve) in the development of inflammation in the muscle, which is one of the key regulators of the inflammatory process in the body. Thus, according to separate studies, it found that vagus nerve stimulation (VNS) reduces the release of pro-inflammatory cytokines during acute inflammation. This effect called the “cholinergic anti-inflammatory pathway.” However, its role in the regulation of muscle inflammation has poorly studied, so further study of its role in inflammation processes is an urgent scientific direction with the aim of possible use as a therapeutic platform for the correction of disorders after exposure to prolonged physical activity. It is important to emphasize that the inflammatory response in muscles in response to physical activity is a complex dynamic system in which a shift in one direction can lead to the development of a hyperimmune response or, on the contrary, reduce it. Therefore, understanding this process, as well as identifying trigger mechanisms, will in the future make it possible to increase not only the effectiveness of the training process, but also to prevent the development of pathological conditions.