BACHGROUND: Epilepsy is a chronic neurological disorder. Despite discovery of effective antiepileptic drugs (AEDs), more than 30% of patients are still resistant to AEDs. OBJECTIVES: Evaluation the effect of acute administration of Docosahexaenoic acid (DHA) in mice resistant to antiepileptic drugs in 6Hz model of epilepsy. METHODS: at first we evaluted intracerebroventricularly (i.c.v) injection and oral consumption of DHA alone and intrapritoneal (i.p.) injection of drugs in separate groups. In test groups LTG 25mg/kg or PHT 25mg/kg were injected i.p. 105 min after injection of PHT, 45 min after injection of LTG, DHA (1mM) was injected i.c.v. In control groups drugs solvent or DHA solvent was injected DHA. 15 min after injection of DHA or DHA solvent, in all groups 6 Hz stimulation was exerted and occurrence of limbic seizures was registered. In oral test groups PHT 25mg/kg or LTG 25mg/kg were injected i.p. 60 min after injection of PHT and simultaneous injection of LTG, DHA (0.1 ml) was gavaged. 60 minutes after injection of DHA 6 Hz stimulation was exerted. RESULTS: Acute administration of DHA alone via i.c.v injection or oral gavage had no protective effect on inhibiting seizures. Administration of DHA with LTG or PHT also couldn’t inhibit drug resistance. 6-Hz seizures when administered chronically. However, chronically administered DHA inhibited limbic seizures resistant to LTG and PHT. CONCLUSIONS: Acute administration of DHA couldn’t inhibits resistance to LTG and phenytoin in 6-Hz model of epilepsy. Also consumption of single dose of DHA with anticonvulsant drugs don’t have any effect on prevention of drug resistance in epileptic patients.