Moreover, our results showed that the ability to learn, memory consolidation, and memory retention in rats with epilepsy improved after acute and chronic treatment with different doses of vitamin D. The results of our study showed that vitamin D could inhibit NF-κB/TNF-α/IL-1β, HMGB1/TLR4/NF-κB, HMGB1/TLR4/IL-1β, and HMGB1/TNF-α pathways and down-regulated the expression of COX-2 and mTOR in hippocampal tissue of epileptic rats. The gene discussed is HMGB1; the disease is epilepsy.