Background Studies show that lack of exercise and physical activity during childhood and teenage years is directly related to different diseases in adulthood. Objectives The main purpose of this study was to investigate the effects of an eight-week aerobic exercise on the quality of life as well as physiological indicators of cardiovascular endurance of inactive high school male students in Kashan. Materials and Methods The study was a field trial using pretest and post-test. Three hundred high school male students in Kashan, Iran, were recruited and interviewed by the researchers, using a questionnaire. Of the inactive ones, 30 who reached the highest criteria standards, were selected as samples and randomly divided to two equal groups. The maximum consumed oxygen (VO2max) and resting heart rate were measured by Quinn aerobic test, and the quality of life was measured by the World Health Organization Quality of Life (WHOQOL-26-Breef) questionnaire. The exercise program included an eight-week aerobic exercise, three times per week, with 60%-75% of the maximum heart beat. During the exercise, the subjects had no other sport activity. To check the normal distribution of the data, Kolmogorov-Smirnov test was used. To evaluate the pretest and post-test results, paired t-test was used and for comparing the groups, independent t-test was applied. All the analyses were performed by SPSS software version 16. Results The mean ages of intervention and control groups were 17.46 ± 1.30 and 17.53 ± 1.18, respectively. The mean weight of the intervention group was 56.73 ± 9.91 kg and its mean body mass index (BMI) was 19.88 ± 3.42. In the control group, the mean weigh and BMI were 60.06 ± 11.96 kg and 20.79 ± 3.51, respectively. The quality of life and its components improved significantly in the intervention group (physical (P = 0.0001), mental (P = 0.0001), social (P = 0.0001), and environmental (P = 0.0001) aspects). VO2max (P = 0.001) and the resting heart beat (P = 0.0001) significantly improved in the intervention group. No significant difference was observed in the control group (P ≥ 0.05). Conclusions Aerobic exercise program improved the quality of life as well as the physiological indicators. Physical activities can be used as both appropriate model and nonpharmaceutical approach to prevent and cure some diseases.