Purpose: To use column chromatography to separate and purify cannabidiol (Cannabidiol, CBD) from hemp leaves, and to explore its application in depressive symptoms. Method: After pretreatment of hemp leaves, supercritical CO2 extraction was used to obtain hemp extract, and the resin was purified in two steps to obtain pure CBD. The establishment of chronic unpredictable mild stress model mice, through intragastric administration of CBD to explore their depression behavior and the influence of inflammatory factors. Results: The purity of CBD extracted by this method was as high as 99.18%; through animal experiments, the CBD dose group significantly improved the depression behavior of model mice (P<0.05;); the expression of TNF-α, IL-1β and iNos mRNA in the cortex and hippocampus of the model group was significantly increased (P<0.05;); the expression of TNF-α, IL-1β and iNos mRNA in the cortex and hippocampus of the CBD dose group were significantly decreased (P<0.05). Conclusion: The CBD prepared by this method has high purity. CBD can effectively improve the depressive behavior of mice and inhibit the inflammatory response in the cerebral cortex and hippocampus.