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ABSTRACT: Depression is a common mental disorder characterized by sadness, loss of interest in activities and by decreased energy. Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. Accumulating evidence has suggested a link between BDNF and depression. Animal studies demonstrated the production of BDNF and its tyrosine protein kinase receptor (trkB). In human studies, the BDNF level and BDNF mRNA in the brain decreased in patients with major depression. Furthermore, several studies demonstrated the serum BDNF levels of patients with major depression were lower than those of a control group, and the BDNF levels correlated negatively to scores for depression. Incidentally, exercise showed the beneficial effects on mental health in depressed sufferers, and recent studies demonstrated that exercise was hypothesized to regulate antidepressant-related mechanisms. Animal studies suggest that exercise may enhance neurobiological processes that increase the BDNF level and BDNF mRNA in the brain of the animals. However, the mechanism remains unresolved at present. Furthermore, there is no consensus on the serum BDNF response to the exercise in humans. We need further studies to examine the associations between serum BDNF level and exercise in depression.