Abstract: Objective To determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy. Methods Epileptic rat models were randomly divided into 4 groups, each being exposed to saline, simvastatin, levetiracetam, or levetiracetam+simvastatin. Brain tissues of the rats were examined. Nissl staining was used to determine pilocarpine-induced neuronal loss in CA1 and CA3 of hippocampus. Western blot was used to detect calpain-1 expression of hippocampus. Results Severe cell death was found 24 h after seizures, with a level significantly higher than the controls. Compared with the saline-treated cells, simvastatin did not decrease severe cell death (\P>0.05), but levetiracetam and levetiracetam+simvastatin decreased severe cell death 24 h after seizures (\P<0.05). No significant differences were found between those treated with levetiracetam and those with levetiracetam+simvastatin. Compared with controls, overexpressed calpain-1 was found in the rats 24 h after seizures, which indicates that calpain-1 may be involved in the pathophysiological mechanisms of epilepsy. Compared with those treated with pilocarpine+saline, simvastatin, levetiracetam and levetiracetam+simvastatin reduced the level of calpain-1 24 h after seizures (\P<0.05). Conclusion Levetiracetam, not simvastatin, possesses neuroprotective properties, through changing calpain-1 expression levels. But levetiracetam plus simvastatin treatment does not have advantages over the choice of monotherapy. Simvastain does not possess neuroprotective properties at the early stage of epilepsy.