Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. The present study was performed to elucidate the relation of HBO exposure time to its oxidative effects in rats' brain cortex tissue. For this purpose, 49 rats were randomly divided into five groups. Except the control group, study groups were subjected to three atmospheres HBO for 30, 60, 90, and 120 min. Their cerebral cortex layer was taken immediately after exposure and used for analysis. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and nitrate-nitrite (NOX) levels were determined. TBARS and SOD levels were found to increase in a time-dependent manner. GSH-Px activity reflected an inconsistent course. NOX levels were found to be increased only in the 120 min exposed group. The results of this study suggests that HBO induced oxidative effects are strongly related with exposure time.