Ｏｂｊｅｃｔｉｖｅ　To investigate the effects of dexmedetomidine(Dex) preconditioning on myocardial expression of high mobility group box-1 protein (HMGB1) during ischemia/reperfusion(I/R) injury in rats.　Methods　Fifty-two healthy male SD rats, weighing 250-300 g, were randomly divided into 4 groups(n=13): group sham operation(group S), group I/R, group Dex+I/R(group D), group Dex+yohimbine+I/R(group D/Y). In group I/R, group D and group D/Y, myocardial I/R was produced by occlusion of left coronary anterior descending artery for 30 min followed by 120 min reperfusion. Blood samples were taken for detecting the concentration of IL-6 and TNF-α by ELISA at the end of reperfusion. The rats were then killed, and the heart was removed for measuring infarct size and area at risk using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Myocardial HMGB1 expressions were measured by Western blot analysis.　Results　Compared with group S, the levels of IL-6［(336±41) ng/L］, TNF-α［(636±25) ng/L］ in serum and the IS/AAR ratio were significantly increased, the expression of HMGB1 were also significantly increased in group I/R(P<0.05). Compared with group I/R, the levels of IL-6［(153±10） ng/L］, TNF-α［（233±9) ng/L］ in serum and the IS/AAR ratio were significantly decreased, and the expression of HMGB1 were also significantly decreased in group D(P<0.05). Compared with group D, the levels of IL-6［(230±20) ng/L］, TNF-α［(386±32) ng/L］ in serum and the IS/AAR ratio were significantly increased, the expression of HMGB1 were also significantly increased in group D/Y(P<0.05). There was no significant difference in the above changes between group I/R and D/Y(P＞0.05).　Conclusions　Dex preconditioning decrease the expression of HMGB1 and alleviate inflammatory response during myocardial ischemia/reperfusion injury(MI/RI） in rats, which might be a result of the α2 adrenergic receptor stimulation.