Abstract: AIM:To validate the effects of physical exercise on the countermeasurement of cardiovascular dysfunction from simulated weightlessness by observing the effects of lower limb muscular exercise and bicycle ergometric exercise during 30-day head-down bed rest (HDBR) and comparing their effects on the changes of orthostatic tolerance, maximal exercise time, body weight and heart rate variability (HRV). METHODS: Fifteen healthy male subjects were randomly and averagely divided into three groups: control group, limb muscular exercise and bicycle ergometric exercise group (five subjects in each group). Subjects in the control group only experienced 30 days -6° HDBR, whereas subjects in the other two groups were trained additionally with low limb muscular exercise or bicycle ergometric exercise, respectively. Orthostatic tolerance and maximal exercise time were measured pre- and post-HDBR. Weight and heart rate variability (HRV) were collected during the entire process of HDBR. RESULTS: On the 30th day of HDBR, orthostatic tolerance decreased significantly (P<0.01) in the control group compared with that pre-HDBR, but no significant decrease was observed in orthostatic tolerance in the limb muscular exercise group and bicycle ergometric exercise group during the same period. On the 30th day of HDBR, maximal exercise time in both control group and limb muscular exercise group decreased significantly (P<0.05), whereas no significant decrease was observed in the bicycle ergometric exercise group compared with that pre-HDBR. Maximal exercise time increased significantly compared with those in control group and limb muscular exercise group (P<0.05). Compared with body weight pre-HDBR, body weight showed a decreasing tendency in the control group and an increasing tendency in the limb muscular exercise group, but no significant changes were observed in bicycle ergometric exercise group during HDBR. On the 10th day of HDBR, body weight increased significantly (P<0.05) in the limb muscular exercise group compared with that in the bicycle ergometric exercise group. Heart rate variability (HRV) analysis found that compared with the indexes pre-HDBR, LFn and LF/HF showed the tendency of decreasing and HFn showed the tendency of increasing in all three groups. CONCLUSION: Thirty-day HDBR significantly decreased orthostatic tolerance and exercise capacity and the balance of cardiac autonomic regulation changes. Limb muscular exercise to some extent increase orthostatic tolerance following simulated microgravity, and bicycle ergometric exercise increased orthostatic tolerance and exercise capacity.