The effect of exercise on depression has long been of interest. Many studies have demonstrated antidepres-sant effect of exercise intervention. They support the belief that exercise has been proven effective in improv-ing depression. By reviewing the relevant published articles, the purpose of this paper is to discuss the possible causality for the effects of exercise on depression. The mechanisms mediating the beneficial effects of exercise on mental health are unknown, although several hypotheses have been put forward. There are many possible explanations to how exercise works to alleviate depression, with some research done on each possible theory. The hypotheses stated so far by scientists are either biological or psychological. In biological classification, biochemical hypotheses are the regulation of chemicals such as hormones in the body or those associated with changes in the nervous system. On the other side, psychological theories cover the possibility of mental differences caused by exercise. In this review article, as part one, the reader are provided with the possible explanation of biological aspects which have been suggested through the literature on antidepressant effects of physical activities and exercise. Among biological assortment which including the physiological and biochemical hypotheses, the put forward hypotheses of catecholamine, endorphin, brain blood flow, Hypothalamus- Pituitary- Adrenal Axis model (HPA), monoamine, and thermogenic/ Pyrogen hypotheses have been discussed. A model that postulates the interplay of biological, psychological, and social factors will be required to explain adequately the mechanisms underlying the effects of physical activity on mental health. Whatever, the reason for the mood enhancing effects of exercise is not necessarily the most important point. The point is that engaging in physical activity has very powerful anti-depressive effects. There may be a combination of these hypotheses that can better explain the causality of the antidepressant effect of exercise.

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