Epilepsy is a prevalent neurological disorder with a high frequency of drug resistance. While significant advancements have been made in drug delivery systems to overcome anti-epileptic drug resistance, efficacies of materials in biological systems have been poorly studied. The purpose of the study was to evaluate the anti-epileptic effects of injectable poly(epsiloncaprolactone) (PCL) microspheres for controlled release of an anticonvulsant, phenytoin (PHT), in an animal model of epilepsy. Methods: PHT-PCL and Blank-PCL microspheres formulated using an oil-in-water (O/W) emulsion solvent evaporation method were evaluated for particle size, encapsulation efficiency, surface morphology and in-vitro drug release profile. Microspheres with the most suitable morphology and release characteristics were subsequently injected into the hippocampus of a rat tetanus toxin model of temporal lobe epilepsy. Electrocorticography (ECoG)from the cerebral cortex were recorded for all animals. The number of seizure events, severity of seizures, and seizure duration were then compared between the two treatment groups. Results: We have shown that small injections of drug-loaded microspheres are biologically tolerated and released PHT can control seizures for the expected period of time that is in accord with in-vitro release data. Conclusion: The study demonstrated the feasibility of polymer-based delivery systems in controlling focal seizures.