Purpose The purpose of this study was to investigate the relationship between physical activity and depression according to the presence of disease. Methods A survey and basic assessment were conducted for 2,754 (Male=1,025 and Female=1,729) aged 40 and over who participated in the rural-based cohort study. The survey included physical activity, depression scale and disease preservation. The basic assessment measured height, weight, and body fat percentage. The measured data were analyzed by using logistic regression to examine the relationship between physical activity and depression prevalence. Results First, physical activity reduced the prevalence of depression by 33% and 51%, respectively, in the general population and in patients with the disease. Second, physical activity once or twice per week reduced the prevalence of depression in patients with disease by 51%, and at least three physical activities reduced the prevalence of depression by 37% in the general population and 33% of patients with disease. Third, physical activity less than 150 minutes per week reduced the prevalence of depression in patients with disease by 43%, and physical activity of more than 150 minutes and less than 300 minutes per week reduced the prevalence of 43% of the general population and 52% of patients with disease. Physical activity over 300 minutes per week had a 38% reduction in the prevalence of depression in the general population. Conclusions This study suggests that the level of physical activity suggested by the ACSM guidelines is appropriate to reduce the prevalence of depression. In addition, the patients with the disease was found to be effective with less frequency and amount of physical activity than the general person.