To understand multidrug resistance gene expression in reactive astrocytes, the present study involved stimulated astrocytes with tumor necrosis factor (TNF)‑α and determined gene expression by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Stimulation induced P‑glycoprotein (gp) and multidrug resistance‑associated protein (MRP0) 1 expression, which peaked by 24 h. Interestingly, the expression of P‑gp and Mrp1 correlated with cell proliferation. Therefore, reactivation of astrocytes may increase P‑gp and Mrp1 expression through TNF‑α and nuclear factor (NF)‑κB signaling. To the best of the authors' knowledge, the present study is the first to demonstrate that in vitro activated astrocytes likely induced P‑gp and Mrp1 expression by increasing NF‑κB expression. The results of the present study provide a novel insight into the mechanism of refractory epilepsy and suggest inhibiting cytokine signaling may block multidrug resistance.