Skeletal muscle regeneration is essential for maintaining healthy muscle function with disease, injury, and aging. Macrophages play a vital role in the regenerative process via pro and anti-inflammatory cytokines that act on the local tissue. The literature surrounding macrophage recruitment post-injury in muscle has primarily focused on monocytes recruited from the blood and infiltrating the tissue, where they differentiate into macrophages. These recruited macrophages are traditionally characterized into pro-inflammatory (M1) and anti-inflammatory (M2) populations. Recent discoveries using genetic fate mapping and single-cell RNA sequencing have aided in discovering distinct tissue-resident macrophage (TRM) populations consistent across various tissues. However, skeletal muscle macrophages have yet to be defined using these advancements. The M1/M2 classification system is an oversimplification of complex in vivo interactions and disregards the role of TRMs. We aim to determine the functional role of TRMs in skeletal muscle. We hypothesize that TRMs expand in regenerating muscle to promote reparative functions. First, we will use genetic fate mapping to track resident macrophages following muscle injury. The depletion of resident macrophages will follow this to determine the loss of function. Additionally, we will track recruited macrophages through other mouse models to better define these populations. Overall, we aim to understand better the role of macrophages in muscle regeneration to help generate therapeutic strategies for improved age-related muscle degeneration and maintenance of muscle function.