Prolonged exposure to hyperbaric oxygen (HBO) can result in central nervous system (CNS) toxicity. The manifestations rang from anxiety, nausea, altered vision, and altered hearing to muscular twitching, unconsciousness, and convulsions. It has been reported that cerebral blood flow (CBF) increases well before the onset of the first seizure, and the abnormal increase in CBF is an important precipitating factor of the seizures [1]. Further studies have shown that nitric oxide (NO), especially that produced by neuronal nitric oxide synthase (nNOS), is responsible for the increases in CBF [2–4]. Meanwhile many studies showed that reactive oxygen species (ROS) can also affect cerebrovascular activity [5, 6], and indeed in the course of HBO exposure, large amounts of ROS are formed [7]. In this study, we investigated the effects of two antioxidants, N-acetylcysteine (NAC) and vitamin E (Vit E), on the CBF during HBO exposure to preliminarily probe if ROS might also play a role in CBF changes during HBO exposure. Male Sprague–Dawley rats were inserted two needle electrodes through the skull to record electroencephalogram (EEG). A fiber optic laser Doppler flowmeter probe fixed by a cylindrical eraser which was cemented to the skull was attached to the surface of dura for CBF measurement. The EEG and CBF were monitored throughout 5 atmosphere absolute (ATA) HBO exposure until the appearance of electrical discharge in EEG and tonic–clonic motions of the head and forelimbs. Latency to seizures was calculated from the moment of pressure reaching 5 ATA to the moment of EEG discharge. The average values at every 1 min interval of CBF were calculated and expressed as percentages of the average value of the 1-min interval prior to the pressure reaching 5 ATA, which was used as the baseline level. Thirty minutes before HBO exposure, rats were injected intraperitoneally with saline or 200 mg/kg NAC, respectively. Vitamin E was orally administrated with the dose of 600 mg/kg. Besides, a nNOS inhibitor, 7-nitroindazole (7-NI), which had been verified to have definite effects to CBF alterations and convulsion induced by HBO exposure, was selected as a positive control at a dose of 30 mg/kg (ip). All results were expressed as mean ± SD and analyzed with repeated ANOVA followed by Fisher’s PLSD. A value of P < 0.05 was accepted as significant for statistical tests. Our results showed HBO exposure could induce CBF increased gradually, and peaked before the onset of seizure at almost 50% above the basal level. 7-NI can downregulate the increase in CBF and markedly extend the latency period. These results were in agreement with previous studies [8]. Meanwhile, the results showed NAC and Vit E could also effectively inhibit the CBF increase that precedes seizures (Figures 1 and 2A). As NAC and Vit E could scavenge ROS, such as O 2 , the present results indicate at least that ROS may also have very important effect on the increase in CBF induced by prolonged HBO exposure.