Objective:The aim of this study was to develop the PLGA nanoparticles (NPs) containing carbamazepine (CBZ) and levetiracetam (LEV) combination (CBZ + LEV) for the treatment of epilepsy and toin vitrocharacterize the prepared NPs. Significance:LEV and CBZ, which are antiepileptic drugs, are used in the treatment of epilepsy. Nano-sized formulations are prepared to use for different purposes such as to improve the solubility/the physicochemical properties and bioavailability of drugs, to decrease their doses and frequency of administration, and to reduce side effects of drugs. Methods:CBZ + LEV-PLGA-NPs were prepared by a modified nanoprecipitation method andin vitroandin vivocharacterized. Also, the antiepileptic effect of the NPs was evaluatedin vivoin a rat epilepsy model. Results:The mean particle size and zeta potential of CBZ + LEV-PLGA-NPs were 180.62 +/- 6.260 nm and -27.08 +/- 3.110 mV, respectively. The values of encapsulation efficiency (EE%) of CBZ and LEV were 51.00 +/- 5.944% and 2.05 +/- 0.367%, respectively. CBZ showed a biphasic release profile with initial burst release followed by a sustained release. Ninety percent of CBZ was released from NPs within two days; however, % LEV release from NPs reached about 80% within 30 min. Conclusion:Our results showed that a decrease in seizure scores in the group treated with CBZ + LEV was observed and also, CBZ + LEV and CBZ + LEV-PLGA-NPs had similar antiepileptic activity. The NPs containing CBZ + LEV might be beneficial in the treatment of epilepsy.