Abstract: Objective To establish a neonatal Tibet minipig model of hypoxic-ischemic encephalopathy and evaluate the magnetic resonance imaging (MRI) manifestations and pathological findings. Methods Six neonatal (1-3 days old) Tibet minipigs were randomized into model group (n=4) and control group (n=2). In model group, hypoxic-ischemic encephalopathy was induced by surgical ligation of the bilateral carotid artery followedimmediately by hypoxic exposure in a hypoxia chamber for 1 h. ESWAN was performed at 2 h, 24 h, 3 days and 5 days after induction of HIE or at 2 h after sham surgery in the control animals to evaluate the brain damage. Conventional MRI scans (T2FLAIR, T2WI, and DWI) were also performed at 24 h after the modeling. Results In the neostriatum, values of T2*-weighted MRI increased and reached the peak level at 3 days post-injury (P<0.05). Subcortical white matter T2* values reached the peak level at 24 h (P<0.05). Neostriatum R2* values were at the lowest level at 3 days (P<0.05). Magnitude values were significantly increased after the model establishment (P<0.05). DWI showed multiple mild focal high signals in the bifrontal subcortical white matter and bilateral neostriatum; T2FLAIR showed slightly increased signal; T2WI showed no obvious abnormalities. SWI showed dilated medulla veins adjacent to the bilateral lateral ventricles and basal ganglia. In the early stage of HIE, brain pathologies were characterized mainly by edema and venous congestion with occasional focal necrosis and hemosiderin deposition. Conclusion ESWAN sequence is capable of detecting bleeding and brain edema, and T2*, R2*, and magnitude values can be used to estimate the changes of brain damage following HIE.