PurposeTo investigate the protective effects of normobaric oxygen (NBO) therapy on acute cerebral ischemia in middle cerebral artery occlusion (MACO) rats using diffusion-weighted imaging (DWI).MethodsA total of twenty adult male Sprague-Dawley rats (280-300 g) of right MCAO model were used in this study. All these MCAO rats were divided into NBO and control group with 10 rats per group. All rats were scanned with DWI sequence of MRI at MCAO 0.5 h, 2 h, 6 h, 12 h, and 24 h. The relative cerebral infarction volume (rCIV) and relative cerebral infarction volume growth rate (rCIVGR) were calculated at all these MCAO time points respectively. The actual ADC value and relative ADC (rADC) of the core (ROI-a), marginal (ROI-b) and peripheral areas (ROI-c) of acute infarction were measured and calculated respectively. The ADC value, rADC, rCIV and rCIVGR at different MCAO time points were compared between NBO and control group.ResultsNo significant difference were found in rCIV and rCIVGR of all these MCAO time points between NBO and control group (p > 0.05), while significant difference was found in ADC value and rADC of ROI-a at MCAO 0.5 h between two group (**p < 0.01), as well as in the ADC value and rADC of ROI-b from MCAO 2-24 h between two group (**p < 0.01). The ADC value and rADC of ROI-c in NBO group were significantly higher than that of control group at MCAO 2 h, 6 h, 12 h and 24 h (**p < 0.01).ConclusionNBO treatment could protect IP of acute infarct areas and slow down the progress of IP when acute cerebral ischemia happens. The application of DWI technology helps to reveal the protective mechanism of NBO treatment on acute cerebral ischemia, and provides an important theoretical basis and an exploration way for future clinical studies on acute cerebral ischemia.