Epilepsy induces seizures as the result of excessive electrical excitation in the brain. The excitation-inhibition balance (EI balance) of the central nervous system (CNS) is implicated in the pathophysiology of epilepsy. The tryptophan pathway generates several metabolites which modulate glutamatergic neuronal system such as kynurenic acid (KA: NMDA receptor glycine-site antagonist) and quinolinic acid (QA: NMDA receptor agonist). We investigated whether alterations of tryptophan metabolism contribute epileptic seizures by disrupting the EI balance in the CNS. KA attenuated pentylenetetrazol (PTZ)-induced epileptic seizures, but QA exacerbated it. Chronic administration of PTZ exacerbated epileptic seizures and increased expression of kynurenine 3-monooxygenase (KMO, which involved in QA synthesis), but decreased expression of quinolinate phosphoribosyl transferase (QPRT, which involved in QA metabolism) and kynurenine amino transferase (KAT, which involved in KA synthesis). Seizure exacerbation was suppressed in KMO heterozygous knockout mice but exacerbated in QPRT knockout mice. These data suggested that expression changes of tryptophan metabolic enzymes may exacerbate PTZ-induced epileptic seizures, through change in the metabolic balance between KA versus QA.