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Background: Major depressive disorder (MDD) is a common mental illness with high lifetime prevalence.A large number of researches had been performed to investigate brain regions involved in the pathophysiology of MDD.But the results are different from these studies using different neuroimaging methods.Objective To evaluate current evidence from Positron Emission Tomography (PET) studies, we conducted a voxel-based meta-analysis of brain cerebral metabolism in MDD.Methods Data were collected from the following databases: PubMed, China Biological Medicine Database, China National Knowledge Infrastructure, Cochrane Library and Web of Science, with the last report up to April 2012.Voxel-based meta-analyses were performed using the revised activation likelihood estimation (ALE) software (GingerALE 2.0).The resulting ALE map was threshold at p < 0.05 (corrected for multiple comparisons by false discovery rate), and a minimum cluster size of supra threshold voxels exceeding 100 mm3 was imposed.Results Ten whole-brain-based FDG-PET studies in MDD were included in the meta-analysis included 188 MDD patients and 169 healthy controls.ALE analyses showed the brain metabolism in bilateral insula, left lentiform nucleus putamen and extra-nuclear, right caudate and cingulate gyrus were decreased.However, the brain activity in right thalamus pulvinar and declive of posterior lobe, left culmen of vermis in anterior lobe were increased in MDD patients.The results show that volumes the brain regions of decreased are more than that of increased regions.Conclusion Our meta-analysis suggested MDD patients showed a dysfunctional circuit including insula, limbic system, basal ganglia, thalamus, and cerebellum that has been discussed in the pathphysiology of depression.Especially decreased insula activity might play the key roles in the neuropathology of depression.And patients suffer from MDD compensated by an increased metabolism in thalamus and cerebellum.