In the present study, the effects of the two classical antiepileptic drugs, carbamazepine and valproic acid, and the non-classical anti-seizure drug vinpocetine were investigated on the expression of the pro-inflammatory cytokines IL-1b and TNF-a in the hippocampus of rats by PCR or western blot after the administration of one or seven doses. Next, the effects of the anti-seizure drugs were investigated on the rise in cytokine expression induced by lipopolysaccharides (LPS) inoculation in vivo. To validate our methods, the changes induced by the pro-convulsive agents 4-aminopyridine, pentylenetetrazole and pilocarpine were also tested. Finally, the effect of the anti-seizure drugs on seizures and on the concomitant rise in pro-inflammatory cytokine expression induced by 4-aminopyridine was explored. Results show that vinpocetine and carbamazepine reduced the expression of IL-1b and TNF-a from basal conditions, and the increase in both pro-inflammatory cytokines induced by LPS. In contrast, valproic acid failed to reduce both the expression of the cytokines from basal conditions and the rise in IL-1b and TNF-a expression induced by LPS. Tonic-clonic seizures induced either by 4-aminopyridine, pentylenetetrazole or pilocarpine increased the expression of IL-1b and TNF-a markedly. 4-aminopyridine-induced changes were reduced by all the tested anti-seizure drugs, although valproic acid was less effective. We conclude that the anti-seizure drugs, vinpocetine and carbamazepine, whose mechanisms of action involve a decrease in ion channels permeability, also reduce cerebral inflammation.