As a common human disorder, epilepsy affects about 0.5% of the population. In many patients with epilepsy, seizures are well-controlled with currently available anti-epileptic drugs, but around 35% of patients with epilepsy continue to have seizures despite carefully optimized drug treatment. Recently, intrinsic or acquired overexpression of multidrug transporters in the blood-brain barrier has been suggested to result in producing pharmacoresistance in epilepsy, for anti-epileptic drugs concentrations would be reduced to the level that is insufficient to cause anti-epileptic activity. Intranasal administration provides a direct transport pathway to brain tissue that circumvents the blood-brain barrier for many drugs and neuropeptides. These significant conditions support the hypothesis that intranasal anticonvulsive treatment may be a prospective management of intractable epilepsy. Unfortunately, there are few studies on intranasal anticonvulsive treatment conducted in the field of intractable epilepsy. Our hypothesis provides not only a new alternative treatment for intractable epilepsy but also has potential for investigating the mechanisms underlying the development of pharmacoresistance in epilepsy.