Abstract: To investigate the antioxidant effect of Cistanche deserticola extract on D-galactose in aging mice, the experimental animals were divided into blank group, model group, V_C positive group (1.70 mg/10 g), low (1 mg/10 g), medium (2 mg/10 g) and high (4 mg/10 g) dose groups of Cistanche deserticola extract which were administered by gavage for 30 d. The organ indices of liver and brain tissues as well as the activities of glutathione peroxide dismutase (GSH-Px) and superoxide dismutase (SOD) and malondialdehyde (MDA) content in liver and brain tissues and animal serum were determined among each group. The structural changes of liver and brain tissues were observed by hematoxylin-eosinstaining (HE). The results showed that comparing with the model group, the mass of animals in the medication administration group was higher than that in the model group. The indexes of liver and brain organs increased in the low, medium and high dose groups of Cistanche tubulosa extract and V_C positive group (P<0.05). The liver and brain organ indexes of mice in the medium dose group increased most significantly, which were 1.62 and 2.31 times that of the model group. The activities of GSH-Px and SOD of liver, brain tissue and serum of Cistanche tubulosa extract in low, medium and high dose groups increased significantly (P<0.05). The activity of GSH-Px in low-dose liver tissue, medium-dose brain tissue, and high-dose serum increased most significantly, which were 1.37, 1.18, and 1.46 times of the model group, respectively. The activities of SOD of medium dose liver tissue, high dose brain tissue, and medium dose serum increased and the most obvious were 1.11, 1.14, and 1.74 times of the model group, respectively. Liver and brain tissue in the medium and high dose groups of Cistanche tubulosa extract and MDA in serum decreased significantly (P<0.01). Compared with the model group, the MDA of the medium dose liver tissue, high dose brain tissue, medium dose serum decreased most significantly, which decreased by 23.86%, 41.68% and 38.30% respectively. It was found that Cistanche deserticola extract had a protective effect on cellular and structural damage in liver and brain tissues of mice caused by aging. Therefore, it was hypothesized that Cistanche deserticola extract had a good protective effect on D-galactose-induced senescence model mice.