This work evaluated doxycycline (2nd generation tetracycline) protection against pilocarpine-induced convulsions in rats. The animals were treated with doxycycline (Dox: 10 to100 mg/kg, i.p., 7days), 30min before the pilocarpine injection (P: 300mg/kg, i.p.) and observed for cholinergic signs, latencies to the first convulsion and death. Amino acid concentrations, lipid peroxidation and nitrite levels in temporal cortices were determined as well as the radical scavenging activity. Doxycycline increased latencies to the first convulsion and death as compared to the untreated P300 group. It also decreased glutamate and aspartate, increased GABA, blocked nitrite formation, reduced TBARS contents and showed a radical scavenging activity. Finally, doxycycline decreased the number of degenerating neurons (evaluated by fluoro-jade staining) and increased the number of viable neurons (assessed by cresyl violet staining) as compared do the P300 group. The antioxidant effect associated with decreased levels of excitatory and increased levels of inhibitory amino acids could explain the neuroprotective effect of doxycycline.