Several studies on exercise and its effect on cognitive function in human and animal populations have documented the beneficial impact of regular physical activity on maintenance of good cognitive abilities and satisfactory health-related quality of life well into older age. The aim of the study was to evaluate the effects of long-term regular running on metabolic profile and cognitive function in middle-aged men.A total of 24 regularly exercising, middle-age men (Group A), all being members of the Runners Club, and 22 age-matched sedentary subjects (Group B), as the control group, were enrolled in this study. The control group included 8 non-overweight (BMI=23.5±5.2) individuals (Group C) and 14 overweight/obese (BMI=30.7±1.6) subjects (Group D). Serum lipid profile, glucose and homocysteine concentrations were assessed by routine laboratory methods. Subjects' cognitive function was evaluated based on Trail Making Test (TMT) and Digit Symbol Test (DST) scores.In a majority of runners (Group A), the BMI and the parameters of lipid profile (TC, HDL, LDL, TG, glycerol) were close to those recorded in non-overweight controls (Group C) and, in both groups, results were ideally within the reference ranges for healthy male subjects. However, as compared to the whole control group (Group B), which may be considered as an average population sample of sedentary middle-age men, significant differences were observed in BMI and concentrations of TC and LDL, as well as in the pro-atherogenic biomarkers (TC/HDL, LDL/HDL), which were lower in runners. A similar tendency was found in concentrations of TG (independent cardiovascular risk factor), glycerol and TG/HDL ratio (surrogate measure of insulin resistance), however the differences did not reach the level of significance. The level of homocysteine (pro-atherogenic biomarker) was comparable in all groups, and in most cases, within the reference range for male adults. Results of cognitive function tests did not reveal any significant between-group differences. The TMT score was found to be correlated positively (r=0.492, p<0.05), whereas DST score was correlated negatively (r=-0.549, p<0.005), with age. The DST performance, as evaluated in the group of runners (Group A), appeared to be strongly dependent (r=0.809, p<0.005) on the educational level of the subject.These data provided evidence of beneficial effects of a long-term regular endurance running exercise on lipid profile and cardiovascular health in middle-aged men. However, we failed to confirm the findings of a favorable impact of regular physical activity on improvement in cognitive abilities.