Abstract: Vascular smooth muscle cells (VSMCs) possess remarkable plasticity to switch from contractile to synthetic phenotype in response to cellular stimuli, known as " phenotype switching” or " phenotype modulation”. Phenotype switching is a pivotal step in both vascular injury repair and the development of vascular diseases such as hypertension and atherosclerosis. Numerous environmental cues, including growth factors, transcription factors, hypoxia and mechanical stretches, have been proved to affect the phenotype modulation of VSMCs. In addition, Recent investigations have demonstrated that microRNAs participate in VSMCs phenotype switching. Interestingly, a class of stress-sensitive microRNAs involved in regulation of VSMCs phenotype switching have been uncovered. During spaceflight, increased mechanical stretches on cerebral vascular induced by microgravity exposure are considered as a main factor leading to phenotype switching of cerebral VSMCs. A better understanding of microRNAs in VSMCs phenotype switching may provide a potential countermeasure for the post-flight cardiovascular dysfunction.