In many populations like wheelchair and prosthetic users, the soft tissue is subject to excessive or repetitive loading, making it prone to Deep Tissue Injury (DTI). To study the skeletal muscle response to physical stress, numerous in vitro and in vivo models exist. Yet, accuracy, variability, and ethical considerations pose significant trade-offs. Here, we present an ex vivo approach to address these limitations and offer additional quantitative information on cellular damage. In this study, skeletal muscle tissue from Sprague Dawley rats was isolated and transversely loaded. Histological analysis and fluorescence staining demonstrated that the setup was suitable to keep the tissue alive throughout the experimental procedure. Mechanically induced cell damage was readily distinguishable through morphological changes and uptake of a membrane impermeable dye. Our comparably simple experimental setup can be adapted to different loading conditions and tissues to assess the cell response to mechanical loading in future studies.