Objective The aim of this study was to identify the mechanism underlying skeletal muscle atrophyinduced by hypoxia exposure. To this aim, expression levels of different types of skeletal muscle protein synthesis- anddegradation-related genes were compared between rats that had experienced hypoxic exposure and normoxia in a hypoxicfeeding intervention (semi-starvation state). Methods SD rats were divided into a normoxic normal diet group (groupC), a hypoxic normal diet group (group H; oxygen concentration of 12. 4%), or a normoxia-matched diet group (group P;the food intake was matched to that of group H). The body composition of rats was tested by DEXA after the 4-weekintervention. The soleus (SOL) and the extensor digitorum longus (EDL) muscles were collected and weighed. Musclesfiber histology was observed using HE staining, and the muscle fiber cross-sectional area (FCSA) was calculated. Theprotein contents of HIF1α, Akt, p-Akt, and skeletal muscle protein synthesis- and degradation-related genes were detectedusing Western blot. Results 1) Body weight was lower in the group H than group C, but there was no significantdifference between the groups P and C during the intervention period. At the beginning of the intervention, the food intakeof group H (which was the same as group P) was significantly lower than that of the group C, and there was no significantdifference between the two groups. (2) After the intervention, the body weight and muscle mass were significantly lower inthe group H compared to groups C and P; the wet weights of SOL and EDL muscles in the group H were significantly lowerthan those of the group C; and the FCSA of the EDL muscle was significantly lower in the group H than in groups C and P.(3) HIF1α protein contents of the EDL muscle was significantly higher in the group H than group C; the ratio of p-Akt/Akt of the SOL muscle in the groups H and P was significantly lower than that of the group C; mTOR and 4EBP1 proteinlevels in the EDL muscle of group H was significantly lower than group C; atrogin1, MuRF1, and Beclin1 protein levelsand the ratio of LC3II/ I in EDL of the group H were significantly higher than those of the group C, and MuRF1 proteinlevel in the SOL muscle of group H was significantly higher than that of the groups C and P. Conclusions Skeletal muscleatrophy caused by hypoxia is induced by hypoxia-specific factors, showing that decreased synthesis and decomposition ofskeletal muscle proteins, which is manifested by a decrease in skeletal muscle protein synthesis and a decrease in decomposition of fast muscle fibers, rather than a decrease in food intake under hypoxia.