Microgravity has a dramatic impact on human physiology illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for the definition of efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group n=8) and the potential beneficial impact of protein supplementation (BRN group n=8) and of a combined resistance and aerobic training (BRE group n=8). Gene expression profiles were obtained using an in-house made microarray containing 6681 muscles-relevant genes. A two-class statistical analysis was applied on the 2103 genes with consolidated expression. We identified 472 and 207 modified genes respectively for SOL and VL in BRC group. Further clustering approaches identifying relevant biological mechanisms or pathways underlined five main subclusters. Three are composed almost of upregulated genes involved mainly in nucleic acid and protein metabolism and two composed almost of downregulated genes involved in energy metabolism. Exercise countermeasure demonstrated a drastic compensatory effect decreasing the number of differentially-expressed genes by 89 and 96% in SOL and VL. In contrast nutrition countermeasure had a moderate effect and decreased the number of differentially-expressed genes by 40 and 25% in SOL and VL. Our results allowed reporting a systematic global and comprehensive view of long-term woman muscle atrophy and brought new lights and insights for space environment and for women who undergo a long-term clinical bed rest. Biological samples were collected from Pre- and Post- bed rest (BR) soleus and vastus lateralis biopsies of each subject from the three groups (bed rest only: BRC; Exercise: BRE; Nutrition: BRN). six technical replicate values (2 duplicate hybridizations a et b to chips with triplicate spots xxx) were obtained for each skeletal muscle sample. Thus for each subject 12 expression measurements (6 before BR and 6 after BR) were obtained for each muscle.