Objective To investigate the effects of antisense glutamic acid decarboxylase (GAD67) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ). Methods A model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD67 mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD67. The effect of antisense GAD67 ODN on behavior, seizure threshold and EEG recording of kindled rats was examined. Results Antisense GAD67 ODN could inhibit the expression of GAD67 mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges. Conclusion The gene of GAD67 may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD67 gene will have a bright future.