Objective: Ischemic preconditioning (IPC) is an endogenous phenomenon that can induce ischemic tolerance (IT) in variety of organs such as brain. In this study, we examined the intermittent and prolonged dose of normobaric hyperoxia (NBHO) in neurologic deficit scores, NF-kB activity, and TNF-α converting enzyme (TACE) expression. Materials and Methods: The rats were divided to four main groups. First two groups were exposed to HO divided in prolonged (24hrs; PrHO) and intermittent (4h×6 days; InHO) groups. Second two groups acted as control groups and they were exposed to 21% oxygen with the following condition: in the same chamber (room air, RA), continuously (24hrs; Pr RA) and discontinuously (4h×6days; InRA). Each group was subdivided to three subgroups. After 24hrs, first subgroup was subjected to 60mins MCAO followed by 24hrs of reperfusion. Then, IT, induced by InHO and PrHO, was measured by neurologic deficit scores and infarct volume. Second and third subgroups were respectively called sham-operated subgroup and intact subgroup designed to assess the effect of HO on NF-kB activity and TNF-α converting enzyme expression. Results: Our findings indicate that InHO and PrHO are involved in the induction of IT. Pretreatment with InHO and PrHO reduce neurologic deficit scores and infarct volume significantly. InHO and PrHO increase NF-kB activity and TNF-α converting enzyme expression with different degrees. Also, InHO with ischemia increase NF-kB activity and TNF-α converting enzyme expression significantly. Conclusion: Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and PrHO seem partly to exert their effects via increasing NF-kB activity and up regulation of TNF-α converting enzyme.