Background: Major depressive disorder (MDD) is one of the most common disorders in the world, but is generally refractory to antidepressant treatment. However, physical exercise has been demonstrated to improve MDD symptoms, though the mechanism through which this is achieved is not clear. This systematic review and meta-analysis aimed to clarify whether physical exercise increased brain-derived neurotrophic factor (BDNF) in patients with MDD to either establish or rule out this effect as a possible mechanism. Subjects and methods: We searched five electronic databases (PubMed, PsycINFO, CHINAL, Cochran Library, and Japanese Central Review of Medicine) for interventional studies released prior to 24 October 2017, examining the effects of physical exercise on BDNF in patients with MDD that compared the experimental group with an MDD control group. Those studies meeting the inclusion criteria were subjected to a meta-analysis in which changes of BDNF from baseline to post-exercise were quantified, with a standard mean difference and random effect model. Results: Five studies were eligible and included 199 participants. All articles included subjects with severe symptoms; three articles studied inpatient populations. All articles introduced aerobic exercise. We found no significant effect of physical exercise on BDNF levels (Z=0.32, p=0.75), and no heterogeneity (I2=0%). The risk of bias was moderate. Conclusions: We conclude that physical exercise does not significantly increase BDNF in patients with MDD. Thus, while increased BDNF has been shown to be beneficial in patients with MDD, physical exercise likely produces its benefits through a different mechanism. However, the small number of included articles and lack of multiple reviewers increase the risk of the result being a false negative.