Introduction: A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer's disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)- induced memory impairment in rats. Materials and Methods: Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. Results: STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Conclusion: Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits.