Objective To examine the effect of sevoflurane analgesia during hypoxia in neonatal rats on the mitogen-activated protein kinase ( MAPK) signaling pathway. Methods In the model group and sevoflurane group, pregnant rats were administered birth asphyxia models. The model group was administered 50% oxygen by volume, while the sevoflurane group was administered 50% oxygen and 2. 5% sevoflurane. The natural delivery group gave birth spontaneously. The learning and memory abilities of newborn ofFspring were assessed. Serum superoxide dismutase (SOD), malondialdehyde (MDA) levels, and number of Nissl bodies in the CA1 area of the hippocampus in brain tissue were examined. Brain tissue MAPK, B-cell lymphoma-2 gene (Bcl-2), Bcl-2 related X protein (Bax), and cysteine protease-3 (caspase-3) mRNA and protein expression were also examined. Results Compared with the model group, newborn ofFspring in the sevoflurane group showed a longer residence time in the target quadrant, increased number of crossing platforms, increased serum SOD, decreased MDA, increased number of Nissl bodies in the hippocampal CA1 area, and increased expression of Bcl-2 mRNA and protein in brain tissue. Expression of MAPK, Bax, and caspase-3 mRNA and protein was decreased (P< 0.05). Conclusions Sevoflurane labor analgesia can effectively improve hypoxic-ischemic brain damage in neonatal rats. It may play a protective role in the brain by inhibiting the MAPK signaling pathway and in turn inhibiting hippocampal neuron damage.