Although it has long been suggested that lithium has robust neuroplastic actions, and these actions lead to an enhancement on synaptic plasticity, the effects of lithium treatment on synaptic plasticity have been rarely studied. This study examined the effects of sub-chronic lithium treatment on synaptic plasticity in the dentate gyrus (DG) of hippocampal slices in the rats. Young adult rats were intraperitoneally administered a daily dose of 1 mgEq LiCl or saline-vehicle for 14 days. Twelve hours after the last injections, the input/output (I/0) responses of field excitatory postsynaptic potentials (fEPSP) and the long-term potentiation (LTP) of fEPSP and population spikes (PS) were determined in the DG of hippocampal slices prepared from the animals treated with lithium or vehicle. Treatment of lithium for 14 days significantly increased the I/O responses of fEPSP and the LTP of fEPSP and PS. These results indicate that sub-chronic treatment of lithium increases the excitatory postsynaptic responses, synaptic strength and the cell firing of the granule cells in the DG of the hippocampus.