Abstract: With the development of China’s aerospace industry, much attention has been paid to the influence of weightlessness on human physiological functions. Cardiovascular deconditioning to microgravity may have adverse effects on the health and work efficiency of astronauts. Post-space flight orthostatic intolerance or PSOI is one of the common adverse effects after astronaouts’ re-enters the gravity field from weightlessness. Recent studies suggest that the occurrence of PSOI may be related to multiple factors such as fluid redistribution, hypovolemia, cardiac atrophy, increased venous compliance, low peripheral resistance, abnormal cerebral blood flow regulation, impaired autonomic nerve and baroreflex, and vestibular dysfunction. This article reviews the relevant mechanisms and possible countermeasures.