To investigate the changes of LTP in hippocampal CA1 region induced by chronic stress and theeffect of phenytoin on them, thirty-two adult male Sprague-Dawley rats were randomly divided equally intofour groups: control group, control-phenytoin group, stress-saline group and stress-phenytoin group. Isolatedhippocampal slices of rats were used to observe the changes of long-term potentiation (LTP) in hippocampalCA1 field using electrophysiological technique. Amplitude of population spike (PS) and field excitatorypostsynaptic 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 andfEPSPs slope in CA1 field were observed. The results showed that the LTP induction rate, the increases of PSamplitude and fEPSPs slope after HFS in control and stress-phenytoin groups were significantly greater thanthose in stress-saline group (P＜0.05). There were no significant differences between control group and stress-phenytoin group or between control and control-phenytoin groups in these indexes (P＞0.05). It is suggestedthat chronic stress can damage the development of LTP in hippocampal CA1 field, while phenytoin canprotect the LTP of stressed hippocampal slices in normal state.