Abstract: OBJECTIVE To explore the protective effect and its mechanism of etomidate on myocardial injury in ischemia-reperfusion(I/R) model rats. METHODS Rats were randomly divided into five groups:sham operation group, model group(I/R group), I/R + etomidate(5 mg·kg^-1), I/R + etomidate(10 mg·kg^-1) and I/R + etomidate(20 mg·kg^-1) group. I/R injury model was established by coronary artery ligation. The treatment group received intraperitoneal injection of etomidate at the corresponding dose, and the sham operation group and the I/R group received the same amount of saline once a day for 14 consecutive days. HE staining was used to observe myocardial injury in rats. Cardiac injury markerscardiac troponin I(cTnI), creatine kinase-MB(CK-MB), myoglobin(Mb) and oxidative stress factormalondialdehyde(MDA), superoxide dismutase (SOD), lactate dehydrogenase(LDH) were detected by ELISA. TUNEL staining was used to detect myocardial apoptosis. Western blotting was used to detect the expression of apoptotic protein Bcl-2 and Bax, the phosphorylation of P65 and protein expression of its downstream target genes IL-1β and TNF-α. RESULTS Etomidate could improve the degree of myocardial injury in rats with I/R and decrease the expression of cTnI, CK-MB, Mb in dose-dependent manner(P<0.05), and increase SOD activity(P<0.05), decrease LDH, MDA content(P<0.05), down-regulate Bax(P<0.05) while up-regulate Bcl-2(P<0.05) protein expression, decrease myocardial apoptosis level(P<0.05), inhibit phosphorylation of NF-kB P65(P<0.05) and protein expression level of downstream target genes IL-1β and TNF-α(P<0.05). CONCLUSION Etomidate has protective effect on myocardial injury induced by I/R in rats, and its mechanism is related to alleviating oxidative stress and inhibiting phosphorylation of NF-kB P65.