Abstract: Objective To observe the influence of intermittent strong stimulation and chronic persistent mild stimulation on the levels of nitric oxide(NO) and endothelin 1(ET-1) in senile rats. Methods A total of 24 senile Wistar rats were randomly divided into the control group,continuous strong stimulation intervention group,chronic persistent mild stimulation intervention group.After the feeding on adaptability,the continuous strong stimulation intervention group received strong stimulation while the chronic persistent mild stimulation intervention group received the mild stimulation,the stimulation in both groups including water swimming,thermal stimulation,fasting,ban water,tail clip,day and night upside down,high-speed horizontal shaking,and flashing light illuminate were performed for 56 days.The change of body weight and preference for sugar were observed;while the levels of vascular active substances such as NO and ET1 were tested. Results After the stimulation,the weight increase and preference for sugar in both stimulation intervention groups decreased not obviously as compared with the control group(P＞0.05).The levels of NO and ET-1 increased obviously in the chronic persistent mild stimulation intervention group when compared with the control group(P＜0.05). Conclusion Every kinds of stimulations will cause the depression in the senile rats,and affect the levels of NO and ET-1,which plays an important role in the pathogenesis and prognosis of cardiovascular disease.