Abstract: OBJECTIVE To investigate the efficacy of Coptidis Rhizoma combined with antiepileptic drugs on epilepsy and the effect of Coptidis Rhizoma on the passing of antiepileptic drugs through blood-brain barrier mediated by P-glycoprotein, thus evaluate the preventive and therapeutic effect of Coptidis Rhizoma on epilepsy. METHODS Verapamil as a P-glycoprotein inhibitor and carbamazepine as a common antiepileptic drug were selected. The mice epilepsy models were prepared by pentylenetetrazole and strychnine, respectively. The seizure latency, convulsion rate and mortality of the mice intragastrically administrated carbamazepine alone or with low, middle and high dose of Rhizoma Coptidis were observed and contrasted. Mice were divided into groups and orally administrated carbamazepine, carbamazepine with Coptidis Rhizoma and carbamazepine with verapamil, and then the brain concentration of carbamazepine was determined and compared. RESULTS Coptidis Rhizoma significantly enhanced the antagonism of carbamazepine to pentylenetetrazole and strychnine, which prolonged the seizure latency and reduced the convulsion rate(P<0.05). The brain concentration of carbamazepine was also markedly raised by Coptidis Rhizoma(P<0.05). CONCLUSION Coptidis Rhizoma has good synergetic effect on the treatment of epilepsy.