A unique characteristic of skeletal muscle is its diversity, reflected in the fibre type composition of muscles and in the heterogeneity of different fibre types. Mammalian skeletal muscle has a remarkable capacity to accommodate to new functional demands, and a high degree of molecular variability is involved in the phenotypic determination of fibre structure, metabolism and contractility. Although this adaptive potential is well established, the signalling pathways linking muscle activity to expression of muscle specific genes, the excitation-transcription coupling, is poorly understood. This work presents peroxisome proliferator-activated receptor ä (PPARä) as a possible mediator in the signalling network regulating metabolic and contractile properties of adult skeletal muscle fibres. PPARs are fatty acid activated transcription factors playing important regulatory roles in development and metabolism. PPARä is known to regulate â-oxidation of fatty acids in muscle and adipose tissue, but has recently also been implicated in the excitation-transcription coupling by studies in transgenic animals. The aim of this work was to investigate wild type expression patterns of PPARä and effects of an active PPARä in skeletal muscles of adult rats, in order to elucidate a possible role for PPARä in adult muscle adaptation. In this gain-of-function study, a transgene encoding an intrinsically active fusion protein of a VP16 activation domain and PPARä (VP16-PPARä) was transfected into the “fast” extensor digitorum longus (EDL) muscle of rat by in vivo electroporation. Succinate dehydrogenase (SDH) activity, cross sectional area (CSA) and myosin heavy chain (MyHC) fibre type distribution among the transfected fibres were analysed, and compared to sham transfected and normal controls. In the second part of this study, expression patterns of the wild type PPARä protein were analysed by immunohistochemistry in normal, untreated soleus and EDL muscles. Overexpression of an active PPARä in EDL muscle fibres of adult rats resulted in reductions of CSAs and increased SDH activity levels, followed by changes in MyHC expression in slow direction. Immunohistochemical data from normal muscles indicated higher levels of PPARä in nuclei of slow/oxidative fibres than in fast/glycolytic fibres, which had higher cytosolic levels. These results support the hypothesis of a role for PPARä in maintaining and transforming muscle fibres in the slow/oxidative direction, for example during endurance training, but also indicate nuclear translocation as a new level of regulation.