AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat liver.METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.