Epilepsy is a common neurological disorder. Because its underlying mechanisms remain incompletely understood, current treatments are not adequate for all epilepsy patients, and some patients progress to refractory epilepsy. Under physiological conditions, excitatory and inhibitory neurons function in a dynamic balance. Epilepsy develops when this balance is disrupted. Intersectin1-L is a major scaffold protein in the central nervous system that contains multiple functional domains, and it is the long form of intersectin1. Recent studies have shown that intersectin1-L plays an important role in the process of neurotransmitter release. In this study, we investigated the expression pattern and distribution of intersectin1-L in patients with refractory epilepsy, in a rat model of pilocarpine-induced epilepsy, and in a rat model of amygdala-kindled epilepsy by immunohistochemistry, immunofluorescence, and Western blotting. The purpose of this study was to explore the relationship between epilepsy and intersectin1-L. The results showed that the intersectin1-L protein was primarily expressed in neurons in brain tissue. Its expression was remarkably increased in patients with refractory epilepsy and in epilepsy model rats. These results suggest that the abnormal expression of the intersectin1-L protein in epileptic brain tissue may play an important role in epilepsy, especially refractory epilepsy.