Recent studies have reported that immune cells were not always found in brain specimens from epileptic patients, then should we stop investigating the relationship between these cells and epilepsy? The answer is no! In addition to immunocyte infiltration in brain parenchyma, a flurry of papers have demonstrated that there were significant alterations in peripheral blood cells (PBCs) immediately after seizure onset, especially changes in some specific transporters of neurotransmitters expressed on the membrane of immunocyte. These transporters may regulate neuronal excitability in mature neurons. Besides, many researchers did find activated leukocytes adhered to the endothelium of blood brain barrier or infiltrated into the brain parenchyma in several types of epilepsy both in human and animal studies; moreover, it is worth noting that different immune cells play different roles in epilepsy development, which was indicated by in vitro and in vivo evidence. This review is going to summarize available evidence supporting changes in PBCs after seizures, and will also focus on some specific effects of immune cells on epilepsy development.