Background: Acquired immune deficiency syndrome is an epidemic in various communities caused by the Human Immuno deficiency Virus (HIV) and exposes people to opportunistic infections and various malignancies. Studies show increase in neurological disorders in people with AIDS. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays an important role in survival, differentiation and cognitive function. Serum BDNF levels have been shown to decrease in HIV patients. Therefore, decreased BDNF levels may be a risk factor for exacerbating neurological disorders in people with AIDS. In addition, studies show that people living with HIV have more psychological disorders that affect their quality of life. Exercise is a treatment strategy performed by people living with HIV as well as rehabilitation professionals to reduce disorders and improve or maintain the health of people living with HIV. Several studies have examined the effect of exercise on quality of life in patients with human immunodeficiency virus infection HIV. Some studies have reported significant positive changes in the quality of life of people with HIV after exercise therapy. Also have been reported increased BDNF levels following exercise in patients with cognitive impairment and neurological disease. Considering the important role of exercise training in health and prevention and treatment of diseases, especially HIV, it seems that the study of the effects of exercise in these patients is of great importance, Therefore, the aim of this study was to investigate the effect of training on level of BDNF level and quality of life in HIV-infected patients. Methods: This is a semi-experimental study. The statistical population of this study consisted of all patients with human immunodeficiency virus infection in the Public health department in Islamshahr, Iran who were invited to participate in this study. 30 AIDS patients were targeted and accessible selected and randomly divided into two groups; combined training and control. The combined training program was run for 12 weeks and 3 sessions per week. Aerobic training involves walking or jogging on the treadmill with a rising intensity and duration of 40% to 65% of maximum heart rate and a duration of 30-60 minutes. Also, Strength training includes 2 to 4 sets and 12 to 20 repetitions per isotonic device in the range of 40% to 60% 1RM. Serum BDNF levels were measured using the ELISA kit, also Quality of life was measured by SF36 health questionnaires. Data were analyzed by independent and dependent t-test at the p<0. 05. Results: The results showed that after 12 weeks of combined exercise the level of BDNF in acquired immunodeficiency (AIDS) patients decreased non-significantly (p=0. 451), also combined exercise significantly improved the quality of life in patients with acquired immunodeficiency (p=0. 037). Conclusion: The findings of the present study show that regular combination exercise can prevent further reduction of BDNF levels in HIV patients, so it may play an important role in reducing central nervous system disorders in these patients. The findings of this study were consistent with the results of Previous research. Various mechanisms that alter BDNF levels are the production of IGF1, neurochemicals such as corticosteroids, intensity of training, age, increased neural activity, or altered activity patterns during exercise. HIV is associated with increased stress, and these patients are exposed to increased levels of stress hormones, so it is possible that increased stress hormones reduce BDNF levels. One of the important reasons for improving the quality of life is increasing patients' self-confidence and ability to overcome special circumstances as a result of comprehensive patient support in the exercise program. Also, exercise can increase the quality of life by increasing exercise capacity and improving mood. Exercise is effective in the mental health of HIV patients and increases confidence, health, feelings of intimacy and happiness, with reducing depression and anxiety and overall increases the quality of life of patients. There were some limitations in the present study, such as the lack of measurement of other cognitive factors. Measurement of endocrine factors, catecholamines, and the internal opioid system after exercise can also help to better explain and interpret the results in HIV-infected patients. According to the results, it seems that regular combined exercise can prevent further decrease of BDNF levels in HIV patients and as a behavioral intervention and complementary therapy play an important role in improving the quality of life of patients. Therefore, it is recommended that HIV patients benefit of regular combination training.