PURPOSE: To research the effects of resistance training on skeletal muscle at hypoxia and Akt-FoxO1 pathway regulatory role during this process. METHODS: 40 male Sprague-dawley rats were divided into four groups randomly and were raised at normoxia and hypoxia (12.4% O2) respectively. Two groups were trained to climb ladder (height 1.2m, inclined at 85°) with load every other day lasting 4-week. Other two groups were quiet control group. Body composition was tested by using DEXA. Isolated extensor digitorum longus (EDL), becips and soleus were made HE stained paraffin section to analyze muscle fibre cross section area (CSA). Total protein and RNA were abstracted to detect Akt, FoxO1, FoxO1 (S256) and downstream E3 ligase (MuRF1 and Atrogin-1) transcription and expression level. RESULTS: Rats lean body mass and CSA of EDL and soleus were decreased significantly(P<0.05 and P<0.05) after 4-week hypoxic exposure. Akt and FoxO1 (S256) expression were decreased, while the expression of FoxO1, MuRF1 and Atrogin-1 were increased (P<0.05). Relatively, resistance training could effectively reduce this atrophy and stimulate rat biceps and EDL hypertrophy (P<0.05 and P<0.05). Meanwhile, Akt and FoxO1(S256) expression were higher than hypoxia training group (P<0.05 ). CONCLUSIONS: Akt-FoxO1 pathway plays an important role in regulating muscle protein during resistance training in hypoxia. Akt activation lead to the nuclear exclusion of phosphorylated FoxO1, which is an important mechanism of resistance training alleviate muscle atrophy.