This study highlights the gender-specific differences in muscular fatty infiltration following rotator cuff tears (RCT), a condition impairing shoulder function more severely in females than in males. The research identifies that these disparities are due to variations in the mTOR/ULK1-mediated autophagy of fibro/adipogenic progenitors (FAPs), which are the primary source of this fatty infiltration. In females, reduced autophagic activity leads to increased adipogenic differentiation of FAPs post-RCT. Importantly, the study introduces metformin as a potential non-invasive treatment. Metformin is shown to enhance the autophagic process in FAPs, thereby reducing fatty infiltration and improving shoulder functionality after RCT. This discovery not only sheds light on the mechanisms behind gender differences in post-RCT muscular fatty infiltration but also suggests a promising therapeutic avenue with metformin to address this issue.