Nod-like receptors (NLRs) are part of the innate immune system, but they are also found in many other cell types, and their role in skeletal muscle remains largely underexplored. To address this, we developed a reproducible treadmill-based acute exercise model in mice, conducted at Zeitgeber Time 16 (ZT16) to align with their active nocturnal phase. Muscle samples were collected from the gastrocnemius at 4-, 8-, and 24-hours post-exercise to capture immediate and delayed gene expression responses. The aim of this thesis was to investigate the role of NLRs in muscle function by assessing how acute exercise affects the expression of NOD1 and NOD2 in skeletal muscle and comparing their expression between males and females. Gene expression analysis using qPCR confirmed that the early response gene NR4A3 was significantly upregulated at 4 hours in both male and female mice, indicating successful activation of exercise-responsive pathways. NOD2 expression was significantly elevated at 8 hours post-exercise in males only, suggesting a sex-specific activation possibly linked to cellular stress and the release of DAMPs following muscle damage. The downstream signalling molecule RIPK2, which is activated by NOD2, was also upregulated in males at 24 hours, further supporting this pathway's involvement. In contrast, NOD1 expression remained unchanged in both sexes. These results suggest that acute exercise triggers sex-specific molecular responses in skeletal muscle, particularly involving NOD2 signalling pathways. The study highlights the importance of considering biological sex in experiments investigating immune and exercise-related gene expression in skeletal muscle tissue.