Objective To investigate the changes of short- and long-term cognitive function and nicotinic acetylcholine receptor (nAChR) function in neonatal rats after etomidate anesthesia.Methods The 7-day-old newborn rats were randomly divided into control group (n = 16), etomidate group (n = 16), and agonist group (n =16), and each group was given a single intraperitoneal injection of 10 mL/kg saline, 5 mg/kg etomidate, and 5 mg/kg etomidate plus 5 mg/kg PNU-282987, respectively. Two hours and 4 weeks after recovering from anesthesia, 8 rats from each group were randomly selected for behavioral tests, after which the bilateral hippocampal tissues were obtained immediately. The mRNA and protein expression of α7nAChR and acetylcholine esterase (AchE) in the hippocampal tissues was detected via RT-qPCR and Western blot.Results Two hours after recovering from the anesthesia, the frequency of head dipping through the holes in the hole-board test in the etomidate group was higher than that in the control group and the agonist group (P < 0.05), while there was no significant difference in the number of correct responses and the total response time throughout the day in the Y electric maze test among the three groups (P > 0.05). Four weeks after recovering from the anesthesia, there was no significant difference in the frequency of head dipping through the holes in the hole-board test, and the number of correct responses and the total response time throughout the day in the Y electric maze test among the three groups (P > 0.05). Two hours after recovering from anesthesia, the mRNA expression of α7nAChR in hippocampus of etomidate group was lower than that of control group and agonist group (P < 0.05), while the mRNA and protein expression of AChE in hippocampus of etomidate group was higher than that of control group and agonist group (P < 0.05). Four weeks after recovering from the anesthesia, there were no significant differences in the relative expression of α7nAChR and AChE mRNA and protein among the three groups (P > 0.05).Conclusions Etomidate anesthesia has no significant effect on short-term learning and memory ability and long-term cognitive ability, but it can temporarily affect the short-term exploration ability of neonatal rats. The mechanism may be related to the inhibition of hippocampal nAChR function.