Abstract. This study evaluated the influence of long-term simulated microgravity on oxidative stress and total antioxidant capacity in the plasma and lung tissues of rhesus macaque (-10°C head-down tilting). Fifteen healthy male rhesus macaques were randomly divided into groups 1 (control, n=5), groups 2 (head-down tilting for 6 weeks, n=5) and groups 3 (head-down tilting for 6 weeks and recover from 4 weeks, n=5). Oxidative stress was evaluated by critical SOD, GSH, H 2 O 2 in plasma and SOD, GSH in lung tissues. HE staining was used to observe the histopathological structure changes of pulmonary tissues. CAT, SOD1, SOD2, SOD3, GPX1, GPX4, GPX7, PRDX1, HMOX1, ALOX5 and DUOX1 mRNA were measured by real-time PCR. GSH concentration was significantly decreased, whereas H 2 O 2 level was significantly increased in group 2 compared with group 1 and group 3. Compared to group 1, histopathological examination revealed alveolar septal thickening, and alveolar and interstitial lymphocytic infiltration in group 2 and group 3 and the pathological changes in group 3 were smaller than those in group 2. Group 2 and group 3 showed significant up-regulation of SOD3 gene compared with group 1 by real-time PCR. In a long-term simulated microgravity environment, systemic antioxidant level of GSH was reduced but an oxidative stress marker of H 2 O 2 was increased. Meanwhile, long-term simulated microgravity caused lung injury and induced the mRNA of SOD3 expression in lung tissues. But oxidant stress is not a major factor involved in the development of lung damage under simulated microgravity. Further study still clarifies the mechanism about the lung injury under microgravity.