An animal model of hypoxic-ischemic encephalopathy (HIE) in newborn pigs was set up to study the histopathological changes of brain injury by light- and electron-microscopy, the changes in total calcium content and calcium iron of RBC, and the effects of two different doses of Nimodipine on HIE. Sixty-one newborn pigs were randomly divided into seven groups, the normal control group (n = 9); the HIE 1-hour group (n = 8) and 24-hour group (n = 8); HIE+ Nimodipine (1 microgram/kg.min-1) 1-hour group (n = 8) and 24-hour group (n = 8). The results showed that these were apparent brain edema, hematencephalon, neuron necrosis, and intracellular body degeneration in the HIE 1-hour group. The levels of RBC TCa and RBC Cai2+ in the HIE 1-hour group were significantly higher than those in the normal control group (P < 0.01). The brain tissues in all groups treated with Nimodipine showed histopathological betterment Compared with the HIE groups. The levels of RBC TCa and RBC Cai2+ in the Nimodipine treatment groups were significantly lower than those in HIE groups (P < 0.01) and were close to the levels in the normal control group (P < 0.05). The authors suggested that early application of Nimodipine in case of postnatal asphyxia might protect the newborn from severe hypoxicischemic brain lesions.