Recent studies documented that administration of PPAR agonists enhances fatty acid oxidation in rodent and human skeletal muscle and that muscle-restricted PPAR overexpression affects muscle metabolic profile by increasing oxidative myofiber number. To date, whether the PPAR agonists altered muscle morphology in adult animals remains unknown. This was examined in this study where adult mice were treated with a PPAR agonist and resulting changes in myofiber metabolic phenotype and angiogenesis were quantified in tibialis anterior muscle. The findings documented a muscle remodeling completed within 2 days and characterized by a 1.63-fold increase in oxidative fiber number and by a 1.55-fold increase in capillary number. These changes were associated with a quick and transient up-regulation of myogenic and angiogenic markers, that precedes induction of PPAR-target genes implicated in metabolism, such as PDK4 and FAT/CD36. Both myogenic and angiogenic components of the remodeling were dependent on the calcineurin pathway as they were blunted by cyclosporine A administration. In conclusion the data indicate that PPAR activation is associated with a calcineurin dependent remodeling of muscle morphology that enhances the oxidative phenotype.