A unique environmental condition of low atmospheric pressure occurs at high altitude which results in decreased partial pressure of oxygen (hypobaric hypoxia) available to lungs in turn leading to low oxygen supply to all organs. The brain is quite hypoxia sensitive organ among all owing to its greater energy demands.1 Human exposure to high altitude leads to decreased physical and mental performance.2 Reports suggests the involvement of corpus callosum3 and hippocampus region4 of brain in high altitude pathophysiology. There are limited reports on understanding of changes in water diffusion in brain due to high altitude exposure. Diffusion Weighted Imaging is a powerful in vivo tool to understand water diffusion under pathophysiological conditions. This study in turn may help in setting new insights to address high altitude related problems effectively.Six SD male rats (11-12 weeks old) were exposed to hypobaric hypoxia equivalent to 22,000 feet above sea level in climatic chamber for 48 hours with temperature and humidity regulated at 25±1⁰C & 55±1% respectively. Diffusion weighted imaging [DTIEPI sequence: TR/TE = 3800 ms/31ms, number of gradient encoding directions = 46, b= 670 s mm-2, matrix = 128×128, field-of-view = 4cm, slice thickness =0.7 mm and number of slices = 15 (contiguous)] experiments were carried out before (control) and after (D0) hypobaric hypoxia of 48 hours. The follow-up MRI scans were also acquired after one day (D1), four days (D4), seven days (D7) and fourteen days (D14). ADC calculation was done by placing ROI at Corpus Callosum (CC), hippocampal layers such as CA1, CA2/3 and Dentate gyrus (Dg) using in house built JAVA based software.5 Changes in apparent diffusion coefficient (ADC) values of the regions of CC and Hippocampal layers in response to hypobaric hypoxia was plotted against time and expressed as means ± SD (Fig-2). Changes in ADC values of each region between pre and post exposure for each group were compared by one-way repeated-measures ANOVA followed by an all-pairwise Bonferroni’s multiple comparison post hoc test (Sigmaplot).A significant increase in ADC values of corpus callosum (CC) was found immediately after acute HH exposure, while no change was observed in the follow-up study. This incremented ADC values of the corpus callosum suggests the occurrence of reversible vasogenic edema, which is in accordance with previous studies on high altitude climbers.2 The CA1 region of hippocampus showed significant decrement in ADC values after one, four and seven day follow-up MRI study, also CA3 and DG showed consistent decrement in ADC values in the follow-up study. This decrease in ADC of hippocampus suggests cytotoxic edema or restrictive water diffusion indicating changes in tissue architecture at micro structural level. In our recent 1H- MRS study of hippocampus region, neuro-metabolic alterations were observed in response to acute HH exposure, which also indicated cellular swelling and compromised neuro-structural architecture.4 Thus, this study presents a potential rat model for risk assessment, early diagnosis & developing interventions to combat high altitude stress with the use of in vivo and non- invasive MRI modalities.Diffusion weighted imaging can be a powerful tool to give an insight of high altitude induced changes in brain areas. The study suggested the occurrence of vasogenic edema in corpus callosum and delayed cytotoxic edema in hippocampus region of brain due to acute high altitude exposure.