Background: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear. Methods: Sixty-four rats were randomly assigned to the control group, the kainic acid (KA) group, the sham-DBS group and the DBS group. Video-electroencephalogram (EEG) was used to monitor seizures. Quantitative real time PCR (qPCR) was applied for detecting interleukin-1 beta (IL-1 beta), IL-1 receptor (IL-1R), IL-6, IL-6 receptor (IL-6R), gp130, tumor necrosis factor-alpha (TNF-alpha), TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2) expression 12 h after the establishment of an epileptic model. The neuronal structural degeneration in the hippocampus was evaluated with transmission electron microscopy (TEM) at this same time point. Results: The seizure frequency was 48.6% lower in the DBS group compared with the sham-DBS group (P < 0.01). The expression of IL-10, IL-1R, IL-6, IL-6R, gp130, TNF-alpha and TNF-R1 was elevated in both the KA and the sham group compared with the control group (all Ps < 0.01). Additionally, ANT-DBS was able to reverse this gene expression pattern in the DBS group compared with the sham-DBS group (all Ps < 0.01). There was no significant difference in TNF-R2 expression among the four groups. The neuronal structural degeneration in the KA group and the sham-DBS group was more severe than that in the control group (injury scores, all Ps < 0.01). ANT-DBS was also capable of relieving the degeneration compared with the sham-DBS group (injury score, P < 0.01). Conclusions: This study demonstrated that ANT-DBS can reduce seizure frequency in the early stage in epileptic rats as well as relieve the pro-inflammatory state and neuronal injury, which may be one of the most effective mechanisms of ANT-DBS against epileptogenesis. (C) 2016 Elsevier B.V. All rights reserved.