Abstract: OBJECTIVE To evaluate the effects of dexmedetomidine on sevoflurane neurotoxicity and the role of ERK1/2 MAPK signaling pathway in the developing brain. METHODS The developmental sevoflurane neurotoxicity model was prepared by exposure of primary hippocampal neurons(7 days in vitro) and Sprague-Dawley rat pups(7 postnatal days) with sevoflurane (3%, 6 h). The cells were treated with dexmedetomidine or combined with U0126. The neuronal apoptosis was analyzed by flow cytometry(FCM) and TUNEL-staining. The relative expressions of total ERK1/2, phospho-ERK1/2, Bax and Bcl-2 were detected by western blot. The spatial learning and memory abilities were determined by Morris water maze. RESULTS Sevoflurane exposure(3%, 6 h) significantly enhanced the neuronal apoptosis(P=0.007), which can be ameliorated by dexmedetomidine(P=0.032). Sevoflurane treatment decreased the expressions of Phospho-ERK1/2 and Bcl-2(P<0.05), but increased Bax(P<0.05). Administration of dexmedetomidine significantly elevated the expressions of phospho-ERK1/2 and Bcl-2, but decreased Bax(P<0.05). The neuronal protective role of dexmedetomidine was abolished by U0126. In addition, treatment with dexmedetomidine significantly improved the cognitive disorders induced by postnatal sevoflurane exposure. CONCLUSION These data indicated that application of dexmedetomidine can prevent sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling pathway may be involved.