To investigate the changes of LTP in hippocampal CA1 region induced by chronic stress and the effect of phenytoin on them, thirty-two adult male Sprague-Dawley rats were randomly divided equally into four groups: control group, control-phenytoin group, stress-saline group and stress-phenytoin group. Isolated hippocampal slices of rats were used to observe the changes of long-term potentiation (LTP) in hippocampal CA1 field using electrophysiological technique. Amplitude of population spike (PS) and field excitatory postsynaptic potentials (fEPSPs) slope were used to indicate the changes of LTP. High-frequency stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3 field, and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. The results showed that the LTP induction rate, the increases of PS amplitude and fEPSPs slope after HFS in control and stress-phenytoin groups were significantly greater than those in stress-saline group (P<0.05). There were no significant differences between control group and stressphenytoin group or between control and control-phenytoin groups in these indexes (P>0.05). It is suggested that chronic stress can damage the development of LTP in hippocampal CA1 field, while phenytoin can protect the LTP of stressed hippocampal slices in normal state.