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Background & Objectives: Postoperative brain damage is a serious problems in cardiac surgery patients. Dexmedetomidine and isoflurane have been reported to have neuroprotective properties in animal. But no report currently compares dexmedetomidine combined with isoflurane and isoflurane anesthesia on brain injury after cardiac surgery. Materials & Methods: 97 patients scheduled for valve replacement surgery with cardiopulmonary bypasses were randomly divided into 2 groups: dexmedetomidine and isoflurane (D-I, n=50) and isoflurane alone (I, n=47). Anesthesia was maintained with either dexmedetomidine and isoflurane or isoflurane alone combined with sufentanil. Dexemedetomidine was infused at 0.6 μg/kg for 15 min as a bolus, followed with 0.2 μg/kg/h until the end of surgery. The inhaled concentration of isoflurane was adjusted to keep the bispectral index (BIS) 40-50 throughout the procedure in both groups. Jugular blood samples were drawn for analysis of matrix metalloproteinase-9(MMP-9) and glial fibrillary acidic protein levels(GFAP) peri-operatively: before induction; 5 min after cardiopulmonary bypass(CPB) onset;after CPB; the first day after operation and the second day after operation. Plasma lactate levels in arterial and jugular venous blood were also quantified at the same five time points. Antisaccadic eye movement(ASEM) test and Mini-Mental State Examination(MMSE) were tested on the day before operation and the seventh day postoperatively. Results: Serum MMP-9 and GFAP concentration increased after CPB and decreased to basal levels on the second morning after surgery in both groups. MMP-9 concentration in group D-I were lower on times of CPB off and the first day after operation. However lower GFAP concentration in group D-I were found on times of 5 min after CPB onset and CPB off. No significant differences were found between the two groups when the difference of arterial and jugular bulb venous blood lactate levels were compared except 5 minutes after CPB on. The MMSE score of total patients was declined significantly from the baseline values of 26.9±1.4 to 25.4±1.5 on the seventh day after operation(p< 0.001). The ASEM scores also decreased significantly from the baseline values of 16.4±3.8 to 13.7±6.8 postoperatively (p< 0.001). No difference were found in postoperative MMSE (p=0.787)and ASEM impairment (p=0.439) between the treatment groups. Conclusion: Dexmedetomidine combined with isoflurane can decrease the biochemical markers of brain injury but does not improve cognitive function after cardiac surgery compared with isoflurane alone.