Exercise stimulates muscle protein fractional synthesis rate (FSR) but the importance of contractile intensity and whether it interplays with feeding is not understood. This was investigated following two distinct resistance exercise (RE) contraction intensities using an intra-subject design in the fasted (n=10) and fed (n=10) states. RE consisted of ten sets of knee-extensions. One leg worked against light-load (LL) at 16% of 1-repetition maximum (1RM), the other leg against heavy-load (HL) at 70% 1RM, with intensities equalized for total lifted load. Males were infused with (13)C-leucine and vastus lateralis biopsies were obtained bi-laterally at rest as well as 1/2, 3, and 51/2 hr after RE. Western blots were run on muscle-lysates and phospho-specific antibodies used to detect phosphorylation status of targets involved in regulation of FSR. The intramuscular collagen FSR was evenly increased following LL- and HL-RE and was not affected by feeding. Myofibrillar FSR was unaffected by LL-RE, whereas HL-RE resulted in a delayed improvement (0.14+/-0.02%xhr(-1), p<0.05). Myofibrillar FSR was increased at rest by feeding (p<0.05) and remained elevated late in the post-exercise period when compared with the fasting condition. The Rp-s6k-4E-BP1- and the MAPk-pathways were activated by the HL intensity and were suggested to be responsible for regulating myofibrillar FSR in response to adequate contractile activity. Feeding predominantly affected Rp-s6k and eEF2 phosphorylations in correspondence with the observed changes in myofibrillar FSR, whereas 4E-BP1 remained to respond only to the heavy load contraction intensity. Thus, the study design allows us to conclude that the MAPk and mTOR dependent signaling responds to contractile activity, whereas elongation mainly was found to respond to feeding. Further, although functionally linked, the contractile and the supportive matrix structures upregulate their protein synthesis rate quite differently in response to feeding and contractile-activity and -intensity.