Chongmyungtang (CMT) is a famous Korean herbal medicine for improving learning and memory, which has been reported to have anti-cholinergic and neuroprotective effects. Therefore, drug-drug interactions were examined between CMT and donepezil as a first screening of combination therapy for cognitive deficits. Rats received oral co-administration of donepezil with distilled water as a control or donepezil with CMT as a combination. The distilled water or CMT was co-administered at intervals within 5min after donepezil or 1.5h intervals. The plasma samples were analyzed for donepezil concentration and its pharmacokinetic parameters of Tmax, Cmax, AUC, t1/2 and MRTinf. In the single co-administration at intervals within 5min, donepezil was detected lower in the combination than control at 0.5h and 2h post-treatment (P<0.05). In addition, the combination showed significant increases in MRTinf compared to the control (P<0.05). This suggests drug-drug interactions between donepezil and CMT in the co-administration within 5 min. However, no meaningful differences were found in the pharmacokinetic profiles of donepezil by single dosing with CMT at 1.5h intervals and even by the repeated dosing for a week at 1.5h intervals potential combination therapy of donepezil with CMT.