Objective To evaluate the effects of cerebral ischemia/reperfusion or/and icariin on expression of cytochrome C oxidase subunitⅡ(COⅡ) mRNA in mice. Methods The mouse model of transient cerebral ischemia/reperfusion was made by bilateral occlusion of common carotid arteries and ischemic hypotension/reperfusion. The mice were divided into several groups at random: normal control group, model group and icariin preventive treatment group (100 mg/kg). The changes in expression levels of COⅡ mRNA in mice cerebral tissue were detected by RT-PCR at different time points. Results The levels of CO Ⅱ mRNA in model group had no significant changes at 1 h and 24 h after cerebral ischemia/reperfusion as compared with that in control group, but decreased remarkably at 3 h (P<0.01), and COⅡ mRNA in the icariin preventive treatment group had no significant changes. At 72 h after cerebral ischemia/reperfusion CO Ⅱ mRNA in model group significantly increased (P<0.01), while pre-treatment with icariin blunted its increasing (P<0.05). CO Ⅱ mRNA in model group dropped at 14 d (P<0.05), and pre-treatment with icariin blunted its decreasing. Conclusion Cerebral ischemia/reperfusion can affect mRNA expression of CO Ⅱ. The pre-treatment with icariin can maintain the expression of CO Ⅱ mRNA, indicating the possible mechanism of the neuroprotective effects of icariin.