AIM: To observe the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its relation with oxidative stress in liver of rats induced by systemic chronic normobaric hypoxia. METHODS: Twenty five male, 6-8 weeks old rats were induced by systemic hypoxia. Rats were divided randomly into 5 groups (n = 5 per group). The control group was exposed to normal environment while the hypoxic groups were kept in hypoxic chamber (10% O(2)) for 1, 3, 7, and 14 days. Animals were sacrificed, the liver isolated and homogenized. Total RNA was extracted and isolated and expression of HIF-1alpha mRNA was measured by real-time RT PCR using Pffafl method. Malondialdehyde (MDA), product of lipid peroxidation was measured by tBARS assay. Glutathione (GSH), an abundant endogenous antioxidant in the liver tissue was measured using Ellman method. RESULTS: Study showed that expression of HIF-1alpha mRNA was increased in group treated for 1 day of hypoxic condition, and then decreased in group treated for 3, 7 and 14 days of hypoxic condition related with duration of hypoxic condition. The MDA level in liver tissue increased, but not significant in all groups of hypoxic condition and persisted along duration time of hypoxic condition. The GSH level was decreased significantly (p<0.005) in all groups of hypoxic condition. CONCLUSION: Expression of HIF-1alpha mRNA was higher at the early phase of hypoxia and decreased as hypoxia continued. Systemic hypoxia induction caused increased ROS formation during hypoxia, and depleted the GSH concentration in the liver. Oxidative stress present in liver of rat was induced by systemic hypoxia.