Objective To study the changes of ERK1/2 phosphorylation status induced by unloading of soleus muscle after tail suspension in rats. Method Hindlimb unloading(HU) was produced by tail suspension, which simulated the effect of weightlessness on male Wistar rats. Western blot technique was introduced to detect the total and phospho-ERK1/2 status in isolated soleus muscle of 7 d, 14 d HU and repective control groups. Result Total ERK1/2 in soleus muscle was not affected by 7 d and 14 d HU. The ERK1 phosphorylation status were declined significantly after 7 d and 14 d HU.The ERK2 phosphorylation status were declined significantly after 7 d HU, but not for 14 d HU. Conclusion The unloading of soleus muscle after simulated microgravity can decrease the phosphorylation status of ERK1/2, which may contribute to the atrophy of soleus muscle induced by simulated weightlessness.