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Objective: To explore the mechanism of Ningshenling Granule in the treatment of depression. Methods: The rat model of depression was established, and Ningshenling Granule was given orally. The morphological changes of hippocampus were observed by HE staining, and the changes of dopamine receptor D2 and CAMK2a mRNA were observed by RT-pcr. Result: Ningshenling group could significantly improve the morphological changes of pyramidal cells in hippocampus and the expressions of D2 and CAMK2a in brain tissue. Conclusions: Ningshenling can treat depression, and its mechanism is related to regulating the expression of related factors in the brain.