Abstract： Objective To investigate the brain perfusion changes in patients with refractory depressive disorder (RDD) and non-refractory depressive disorder (NDD) using arterial spin labeling (ASL).Methods Present study included 12 patients with RDD, 37 patients with NDD and 42 controls,and their age, sex and handedness were matched among the three groups.FAIR sequences were performed using a 3 T MR imaging system with an 8 channel phase array head coiL The labelled and controled images were subtracted and then averaged to obtain perfusion-weighted images.The first 2 images were excluded to avoid T, equilibrium effects and then voxel based analysis was performed using SPM2. One way ANOVA analysis using age as covariance ( thresholded at P ＜ 0.01 uncorrected) was performed.Results Patients with NDD showed regional alteration of the brain perfusion, mainly involved in two frontal subcortical circuits, i.e. significantly decreased perfusion in the left frontal and thalamus (the limbic thalamo-cortical circuit) whereas significantly increased perfusion in bilateral hippocampi, fight lentiform and left anterior cingulated gyros (the limbic-striatal-pallidal-thalamic circuit).In contrast, patients with RDD presented significantly decreased perfusion involving bilateral frontal areas (the limbic-thalamo-cortieal circuit) whereby no significantly increased perfusion areas were observed.Conclusion In addition to the reported experimental evidences, our results suggest that the RDD is associated with inactivity of bilateral frontal areas, while the NDD is associated with inactivity of left frontal areas and overactivity of bilateral limbic system.