Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by iso-flurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial leing and memory ability in adulthood in the fetal rats. Altogether, these findings in-dicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.