P-glyprotein (multidrug resistance gene 1, MDR1) was the first isolated and most extensively investigated refractory epilepsy-related drug-resistant protein. Coriaria lactone (CL) can induce P-glyprotein expression of brain capillary and astrocytes in vivo. We established the primary rat brain microvascular endothelial cell (BMECs) models overexpressing P-glycoprotein induced by CL successfully and infected them with adenovirus vector, which carry small interfering RNA (siRNA) designed to target MDR1b. MDR1b mRNA levels and P-glyprotein expression in experimental group decreased significantly 72 h after infection, and the fluorescence intensity of rhodamine within the cells of experimental group increased significantly. So, CL can induce P-glyprotein overexpression in BMECs in vitro, and siRNA can effectively inhibit expression of P-glyprotein and decrease its "pumping out" function. This may offer a new method and rationale for studying the mechanism of refractory epilepsy and relevant gene therapy.