Objective To study the effect of etomidate on the changes in [Ca2+]i in rat cerebrocortical synaptosomes induced by KCI. Methods Freshly isolated SD rat cerebrocortical synaptosomes were prepared. KCI was used as chemical stimulant. Neurochemical method was employed (Fura-2 was used as calcium indicator) . Etomidate was added (the end concentration was 0.4, 4, 40 and 100 ?mol?L-1 respectively) before and after stimulation with KCI 50 mmol?L-1 to determine the peak and plateau [Ca2+]i in the cerebrocortical synaptomes. Results Before KCI stimulation etomidate inhibited KCl-evoked increase in intra-synaptosomal [Ca2+ ]i in a concentration-dependent manner. The inhibitory ratio of peak calcium concentration was 5%?3% , 11%?6% , 24%?10% and 33%?12% respectively as compared with control. Etomidate at concentration of 40 ?mol?L-1 and above had significant effect on [Ca2+]i. When added immediately after KCI stimulation, 4,40 ?mol?L-1 etomidate significantly increased plateau [Ca2+]i in synaptosomes.Conclusion Etomidate alters KC1-induced calcium dynamics in rat cerebrocortical synaptosomes. Presynaptic calcium channels and calcium removal mechanism are involved in its anesthetic action.