Exercise is beneficial to brain and can attenuate stress-induced hippocampal damages. However, the details involved monoamine neurotransmitter in exercise to counteract stress have not been well elucidated. The aim of this study was to examine exercise-induced responses of the norepinephrine (NE) and serotonin (5-HT) systems in counteracting stress-induced hippocampal damages. Rats were divided into exercise (four weeks of voluntary wheel running), stress (three weeks of restraint stress), exercise-stress (three weeks of stress following four weeks of exercise), and control groups. Levels of NE and 5-HT were detected with high-performance liquid chromatography (HPLC), mRNA expression was detected with real-time fluorescence quantitative reverse transcription polymerase reaction (FQRT-PCR) and proteins associated with 5-HT(subscript 1A) receptors (5-HT(subscript 1A)-R) and β2-adrenergic receptors (β2-AR) were analyzed by Western blotting. Serotonin levels were highest (P ＜ 0.01) in the exercised group, lowest (P ＜ 0.05) in the stressed rats, and were similar (P = 0.065) in stressed and exercise-stressed rats. NE levels were highest (P ＜ 0.01) in the exercised group, and higher in the exercise-stressed than the stressed rats (P ＜ 0.01). Serotonic receptor mRNA expression was highest (P ＜ 0.01) in the exercised group, lowest in the stressed group. The 5-HT(subscript 1A)-R protein expression changed in the same tendency as its mRNA levels. The β2-AR mRNA was highest in exercised rats (P ＜ 0.05), and its protein expression was higher in the exercised and exercise-stress rats than in the control and stress rats (P ＜ 0.05). In conclusion, NE may represent endophenotypic features of exercise states. Serotonin levels may be more susceptible to stress and responsible for deleterious stress-induced effects. NE and 5-HT may both contribute to counteraction of stress-induced hippocampal damages of physical exercises.