It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechano-sensory pathway has been scarce. We here show that in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns isometric contractions induced two-fold more hypertrophy than contractions with 50-60 % of the isometric force. The number of myonuclei and the RNA levels of myogenin and MRF4 were increased with high load, suggesting that activation of satellite cells are mechano-dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load-independent, indicating that the electrical signaling rather than mechano-signaling controls fiber type. Akt and S6K1 were not significantly differentially activated by load, suggesting that the difference in mechanical factors were not important for activating the Akt/mTOR/S6K1-pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent suggesting that mechano-signaling in skeletal muscle is different.