Objective To investigate the ralationshi betueen the frequency of exposure to sevoflurane and neurotoxicity and its effect on neurodevelopmental in rats.Methods Seventy-six SD rats 7 days after birth were divided into four groups according to the random number table method:control group,single exposure to sevoflurane for a single day(S1 group),exposure to sevoflurane for two consecutive days(S2 group),exposure to sevoflurane for three consecutive days(S3 group),each group 19 rats.SD rats were exposed to 2%sevoflurane+50%O2 for 4 hours.The pH value,oxygen partial pressure,carbon dioxide partial pressure,and blood oxygen saturation of each group of rats were recorded.Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining was used to evaluate neuronal apoptosis in the cerebral cortex and hipp-ocampal region.And the cognitive function of rats was explored by Morris water maze test.Results There was no statistically significant increase in the blood gas analysis results among different groups of rats(P>0.05).The number of apoptotic neurons in the cortex of S3 group rats was significantly higher than that in the control group(54.17±13.89 vs.5.67±3.08),the number of apoptotic neurons in the hippocampus of S3 group rats was significantly higher than that in the control group(25.50±8.46 vs.6.17±1.94),the differences were statistically significant(P<0.05).However,there was no statistically significant difference in the number of apoptotic neurons in the cortex and hippocampus of the S1 and S2 groups compared to the control group(P>0.05).The time to search for hidden platforms on the 3rd day of Morris water maze test of S3 group rats was significantly longer than that of the control group[(23.79±10.60)s vs.(13.04±8.83)s],and the percentage of swimming time in the target quadrant on the 6th day was significantly lower than that of the control group[(30.79±4.55)%vs.(40.42±9.92)%],the differ-ences were statistically significant(P<0.05).However,there was no statistically significant difference between the S1 and S2 groups of rats in the time to search for hidden platforms on the 3rd day of Morris water maze test and the percentage of swimming time in the target quadrant on the 6th day compared to the control group(P>0.05).In addition,swim patterns showed that rats in S3 group swam in random circles throughout the pool on the 6th day of Morris water maze test,which was different from other groups.Conclusion Multiple sevoflurane exposure for three consec-utive days is associated with the neurotoxicity in the developing brain and lead to the subsequent neurodevelopmental defects in later life.The pres-ent study also provides an effective animal model for further studies exploring the effects of general anesthetics on developing brain.