Background: Carbonic anhydrases (CAs) are metalloenzymes which catalyze the reversible hydration/dehydration reaction of CO2, in order to maintain the cell homeostasis. These enzymes are found in various tissues and involve in a number of different physiological processes, including ion transport, acid-base balance, bone formation, and gluconeogenesis. Objective: To examine the specific activity of CA and to observe the liver tissue respond to oxidative stress by measured the malondialdehyde (MDA) concentration, in rat liver tissue induced by chronic systemic hypoxia for 1, 3, 5, 7, and 14 days of hypoxia. Results: The study showed that the activity of CA induced by chronic systemic hypoxia significantly increasing at early exposure to the hypoxic condition, at day 1 and days 3 of hypoxia (0.281 and 0.262 nmol/mg protein/minute compared to control 0.155 nmol/mg protein/minute) (p<0.05). No statistical difference at treatments of hypoxia 5, 7, and 14 days. The concentration of MDA also increased significantly on day 3 of liver tissue hypoxia (0.013 nmol/mg compared to control 0.009 nmol/mg liver tissue) (p<0.05), and no statistical differences at day 1, 5, 7, and 14 days of hypoxia. Conclusion: There was damage of membrane cells affected by oxidative stress in the liver tissue of rats induced by chronic systemic hypoxia.