OBJECTIVE To examine whether 30% intralipid could shorten the duration of anesthesia induced by etomidate and its underlying mechanism. METHODS Male Sprague-Dawley rats were anesthetized by etomidate (2.85 mg/kg) through caudal vein. After loss of righting reflex, 40 rats were randomly divided into four groups, each being administered intravenously with 2 mL 30% intralipid, 2 mL normal saline, 0.5 mL 30% intralipid, and 0.5 mL normal saline, respectively. The durations from loss of righting reflex to revival of righting reflex and to normal activities were recorded. In the study in vitro, the mixture containing 30% intralipid (3.03%, 1.52%, 0.76%, 0.37% and 0.00% respectively), rat plasma and 0.066 mg/mL etomidate was vortex mixed and centrifuged. The concentration of etomidate in aqueous phase was determined by high-performance liquid chromatographic (HPLC) method. RESULTS Compared with those of normal saline at a dose of 2 mL, 30% intralipid significantly shortened the duration from loss of righting reflex to revival of righting reflex [(493 +/- 27) s vs. (755 +/- 64) s, P < 0.01) and from loss of righting reflex to normal activities [(643 +/- 36) s vs. (1104 +/- 114) s, P < 0.01] of the rats. Intralipid reduced the concentration of etomidate in aqueous phase in vitro. CONCLUSIONS Intralipid shortens the duration of anesthesia induced by etomidate in rats, possibly through extractive effect of intralipid on etomidate.