Exercise up-regulates the expression of NR4A receptors which are involved in regulation of glucose and fatty acid utilization genes in skeletal muscle. The aims of our study were 1) to determine the role of local contractile activity on NR4A mRNA expression in skeletal muscle during exercise and 2) to elucidate the mechanisms underlying the induction of NR4A mRNA expression in response to muscle contractile activity. Rats were subjected to an acute 3h low-intensity swimming (LIS) or a 3h low-intensity treadmill running (LIR) as a model of endurance exercise. LIS increased NR4A1 and NR4A3 mRNA in triceps but not in soleus muscle. Conversely, LIR increased NR4A1 and NR4A3 mRNA in soleus but not in triceps muscle. NR4As mRNA increased concomitantly with reduced post-exercise muscle glycogen, suggesting that gene expression of NR4A receptors occur in muscles recruited during exercise. Furthermore, in resting rats, an acute 1 h local electrical stimulation of a motor nerve to the tibialis anterior muscle caused increases in NR4A1 and NR4A3 mRNA relative to the contralateral control muscle of the same animals. On the other hand, after 6 h of hindlimb immobilization, NR4A1 and NR4A3 mRNA were reduced in immobilized soleus muscle relative to contralateral control muscle. In addition, both NR4A1 and NR4A3 mRNA in epitrochlearis muscle were increased after 6h incubation with 0.5mM 5-aminoimidazole- 4- carboxamide ribonucleoside (AICAR) which activates AMP-activated protein kinase (AMPK). These results suggest that 1) local muscle contractile activity is required for increased expressions of NR4A1 and NR4A3 mRNA during exercise, 2) muscle contractile activity-induced increases in NR4A1 and NR4A3 mRNA may be mediated by AMPK activation at least in part.