Upon weightlessness and microgravity deleterious effects on the neurosensory and neurovestibular systems haematological changes and deconditioning of musculoskeletal cardiovascular and cardiopulmonary functions have been reported. In particular loss of muscle mass and strength are triggered by weightlessness in humans during space flights that is similarly observed as a result of physical inactivity conditions and aging on Earth. However skeletal muscle tissue is of paramount importance for health maintenance (e.g. being essential to locomotion heat production and metabolism). To better prevent or eventually treat microgravity-induced muscle atrophy its underlying mechanisms have first to be characterized in detail. Using cutting-edge quantitative proteomics the aim of the present study was therefore to get an in depth view of the molecular regulations triggered by space conditions in skeletal muscles of mice during the 30-day flight of the BION-M1 biosatellite. As muscles differing in their fiber type composition appear to respond differently to microgravity (see above) we characterized here the differential response of the soleus extensor digitorum longus and vastus lateralis muscles.