The orphan nuclear receptor 4A subgroup consists of three related nuclear receptors, NR4A1-3. Our previous work on NR4A3 reported that preferential over-expression of activated NR4A3 in mouse skeletal muscle regulates aspects of skeletal muscle that are associated with adaptations following exercise, such as fiber type, running endurance, mitochondria number, glycogen levels, glucose tolerance and metabolic gene expression. Similar metabolic changes have also been observed by the manipulation of NR4A1 in skeletal muscle by other laboratories. Our current work has demonstrated that over-expression of activated NR4A3 in skeletal muscle also results in skeletal muscle hypertrophy and enhanced vascularisation, key physiological consequences of exercise in skeletal muscle. Here we report that mRNA expression of all three members of the orphan nuclear receptor 4A subgroup are transiently increased in response to exercise. Taken together, these results suggest that in response to exercise, that the orphan nuclear receptor 4A subgroup may regulate gene expression that mediates the positive physiological, metabolic and molecular changes that occur following exercise (such as enhanced glucose tolerance). This raises the possibility that the orphan nuclear receptor 4A subgroup could be therapeutically used to treat conditions that improve in response to exercise (such as type 2 diabetes) without the need for exercise.