Objective To investigate the characteristics of regional homogeneity （ReHo） changes in the resting state of brain regions in melancholic depression. Methods A total of 26 patients with melancholic depression attending the First Hospital of Shanxi Medical University from February 2019 to December 2021， and 20 healthy controls were included. All the subjects underwent resting functional magnetic resonance imaging， and the ReHo differences between the two groups were compared. The general data of subjects were collected by self-made affective disorder observation form， and the depression status of MD group was evaluated by 17 item Hamilton Depression Scale （HAMD-17）. Pearson correlation was used to analyze the correlation between ReHo value and HAMD-17 score in different brain regions of MD patients. Results The ReHo values of left fusiform gyrus， putamen and middle occipital gyrus / inferior occipital gyrus in MD group were significantly lower than those in the control group， and the differences were statistically significant （t=-6.392， -4.540， -5.786； P ＜ 0.05）. The ReHo values of the right superior frontal gyrus， precuneus and left middle frontal gyrus / anterior central gyrus in MD group were significantly higher than those in the control group， and the differences were statistically significant （t=4.796， 5.185， 5.111； P ＜ 0.05）. The decrease of ReHo value in left fusiform gyrus in MD group was positively correlated with block symptoms （r=0.397， P＜ 0.05）. The increase of ReHo value in the right precuneus was negatively correlated with HAMD-17 score， block symptoms and sleep disorders （r=-0.452， -0.446， -0.411； P ＜ 0.05）. After further controlling the confounding factors， partial correlation analysis showed that the ReHo value of left fusiform gyrus was positively correlated with blocking symptoms （r=0.437， P＜ 0.05）， and the ReHo value of right precuneus was negatively correlated with HAMD-17 score and sleep disorder （r=-0.568，-0.500； P＜ 0.05）. Conclusions There are spontaneous brain activity abnormalities in multiple brain regions of MD patients， involving default network and reward circuit， which are related to the severity of depression， blocking symptoms and sleep disorders.