1. The study investigated the role of Klotho, an inflammatory protein, in regulating macrophage phenotype and the inflammatory response during skeletal muscle regeneration. 2. Following muscle injury in mice, ablation of Klotho led to increased pro-inflammatory M1 macrophages and decreased regenerative M2 macrophages and eosinophils compared to wild-type mice. 3. The results suggest that Klotho deficiency promotes a prolonged pro-inflammatory environment after injury and impairs the resolution to a regenerative phase marked by M2 macrophages. Klotho may be an important mediator of the inflammatory response and transition to muscle regeneration.