In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.