Objective: To investigate the expression of multidrug resistance gene 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in the refractory epilepsy related to rapamycin-related target protein and the role of two proteins in the process of drug resistance. Methods: Thirty-nine cases of intractable epilepsy with rapamycin target protein were selected, including 9 cases of focal cerebral cortex dysplasia (FCD) type IIB, 15 cases of tuberous sclerosis complex (TSC) and 15 cases of ganglioglioma (GG). We grouped via the lesions type. Ten cases of normal brain tissue were used as the control group. We choose MDR1 and MRP1, which are 2 kinds of immunohistochemical antibodies. We use the MaxVision method to stain, to observe the expression of these 2 antibodies in different groups. Results: The two resistant proteins of MDR1 and MRP1 were all upregulated in the disease group compared with the control group, but the distribution of the cells was different. MDR1 is mainly expressed in the vascular endothelial cells in the focus area. MRP1 is mainly expressed in abnormal neurons in the lesion area, and the expression of balloon like cells and giant cells is different. In addition, 2 kinds of proteins were moderately or more expressed in glial cells, and MRP1 was more clearly expressed in glial cells around vessels. The intensity and extent of expression correlated with the number of glial cells in the lesions. Conclusion: MDR1 and MRP1 are coexpressed in rapamycin related intractable epilepsy (FCD IIB, TSC and GG), and may have roles in the mechanism of drug resistance. Abnormal morphologic neurons, hyperplastic glial cells and damaged vascular endothelium are closely related to the drug resistance of epilepsy.