BACKGROUND: EEG shows a sequence of progressive changes in status epilepticus (SE). Timely antiepileptic drug treatment is an important factor for the prognosis of SE. Here we investigated the effect of treatment according to EEG staging in a lithium-pilocarpine SE rat model. METHODS: By analyzing the on-going EEG of SE, we injected propofol (PF) or propofol and valproate (PF+VA) on each defined EEG stage [early period, merging stage; middle period, continuous stage; late period, early periodic epileptiform discharges stage (ePED)]. We measured the duration of each stage after the treatment and the number of principal cells at three hippocampal areas (CA1, CA3, dentate gyrus] after SE. RESULTS: Both PF- and PF+VA-treated groups showed lower mortality rate in the merging stage-treated subgroup than in ePED-treated subgroup. Seizure duration was significantly shortened in the merging stage of both PF- (p<0.005) and PF+VA-treated groups than in untreated group (p<0.002). The durations of the continuous stage and ePED were shortened in the merging stage-treated subgroup, but ePED duration did not decrease in ePED-treated subgroup. The shortening of the continuous stage and ePED was more prominent in the PF+VA-treated group than in PF-treated group. Neuronal loss in both PF- and PF+VA-treated groups was so severe that CA1 and CA3 neuronal loss was decreased more markedly in the ePED-treated group than in the merging stage-treated group (p<0.01). CONCLUSIONS: Early therapy based on the defined EEG staging might be an effective option for shortening duration of SE and decreasing neuronal damage at the hippocampus. Early combination therapy adopting PF+VA requires further investigation for new treatment option.