Skeletal muscle development requires the expression of myogenic regulator factors MRFs and myosin heavy chain. Resveratrol (RSV), a natural polyphenolic compound found in grapes and red wine, has anti-inflammatory and antioxidant properties. RVS has been shown to alter protein catabolism and muscle function. The mechanisms underlying RVS-induced adaptations in skeletal muscle are unclear. In this work we study the RSV effects during muscle differentiation in C2C12 myoblast cells. We examined the dose-dependent effects of RSV. By Real-time PCR, Western Blot and Immunofluorescence we investigated muscle proteosynthesis and morphologic features in C2C12 myotubes exposed to 0.1 or 25 mM of RSV for different times. RSV induced two activation peaks of AKT/p70S6K and ERK Kinase pathways (5 min; after 8 hours). Treatment with the highest dose of RSV (25 mM) also caused an increase of the AMPK protein content. Then, RSV might control the cell cycle progression through p21/p27 cycline. We showed the positive effectsof RSV on differentiation and hypertrophy process. RSV increased MRFs (Myf6, Myostatin) proteins content. RSV induced hypertrophic morphological changes in neo-formed myotubes, by modulation of cytoskeletal proteins (MyHC, N-Cadherin, Actin and a-Tubulin).Our data suggest that RSV promotes myogenesis and hypertrophy process, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment.