Oxidative stress is a likely molecular mechanism in the neurotoxicity of kainic acid (KA), an excitotoxic substance. The aim of this report was to assess the effect qf melatonin co-treatment against KA by measuring the levels of Coenzyme Q10 (CoQ 10), lipid peroxidation (LPO), and Thioredoxin (Trx) mRNA in the rat hippocampus. The male rats were divided into three groups as saline, KA treatment (15 mg/kg), and KA plus melatonin (20 mg/kg). The levels of LPO and CoQ10 were determined by high pressure liquid chromatography (HPLC) consisting of fluorescence and electro-chemical detectors, respectively. The expression of the Trx gene was quantified using reverse transcription followed by real-time polymerase chain reaction (RT-PCR). The results show that the level of LPO increased although the level of CoQ 10 decreased both in homogenates and mitochondria in KA-treated rats However, melatonin co-treatment attenuated the level of LPO and partially restored the level of CoQ10. Melatonin co-treatment against KA did not affect the regulation of Trx. Finally, in the context of the decreased LPO and the increased CoQ10, the results suggest that melatonin may be protective against central nervous system pathologies involving excitotoxicity or where oxidative damage may contribute to mitochondrial dysfunction.