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Abstract: Objective: To explore protective effects of electroacupuncture at “Nèiguān” (▪ PC 6) for preconditioning on myocardial ischemia-reperfusion injury (MIRI) and the mechanisms involved. Methods: Forty-eight male Wistar rats were randomly divided into a sham operation group (Group N), a MIRI group (Group M) and an electroacupuncture (EA) group (Group E). The MIRI model was established by ligating the left anterior descending artery (LAD) for 30 min followed by reperfusion for 120 min. Partition sutures were passed under LAD without ligation for rats in Group N. Rats in Group E were pretreated with electroacupuncture (EA) applied at bilateral “Nèiguān” (▪ PC 6) for 20 min once a day for 3 consecutive days before ischemia. The infarct size plus the area at risk was evaluated by 2,3,5-triphenyltetrazolium chloride staining, and serum isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) levels were measured by biochemical methods. Myocardium morphological changes were observed under light microscopy. The mRNA expressions of myocardial δ and κ opioid receptors (DOR and KOR) were tested by real-time RT-PCR measurements. Results: The myocardial infarct size in Group E was more significantly decreased than that in Group M (P<0.05). The levels of CK-MB [(980 ± 92) U/L] and LDH [(2743 ± 124) U/L] in Group M were significantly higher than those in Group N [(312±41) U/L] and [(530 ± 56) U/L], respectively (both P<0.01). The levels of CK-MB [(572±70) U/L] and LDH [(1819±97) U/L] in Group E were significantly lower than those in Group M (both P<0.01). There were no significant differences in mRNA expressions of DOR and KOR between Group M and Group N (both P>0.05), but DOR expression in Group E was significantly higher than that either in Group M or in Group N (both P<0.01). No significant differences were found in KOR expression among the three groups (all P>0.05). Conclusion: Up-regulation of expression of δ opioid receptors may be involved in protective effects of EA at Nèiguān (▪ PC 6) for preconditioning on MIRI. [Copyright &y& Elsevier]