Objective To explore the effects and mechanism of different styles of music on the depression-like behavior of rats induced by chronic unpredictable and mild stress (CUMS). Methods We selected 39 depressed rats by sucrose preference tests (SPT) and forced swimming tests (FST). They were randomly divided into Control (no music), Light music, and Classical music groups. The Light music and Classical music groups were introduced to music by Hisaishi and Mozart, respectively, for 4 hours per day for 3 weeks, after which SPT, FST, and O-maze tests were conducted. A pathological change in the hippocampus was observed with HE staining. The expression level of hippocampal BDNF protein was detected by Western blot and immunohistochemical staining. Liquid chromatography-tandem mass spectrometry (LC- MS / MS) was used to measure the content of hippocampal CORT and 5-HT. BDNF, CORT, 5-HT, and IL-1 (interleukin- 1β, IL-1β) levels in serum were determined by ELISA. Results Compared with the Control group, the percentage of sucrose preference was significantly greater (P< 0. 05), the immobile time in FST was significantly less (P< 0. 01), and the time and staying time in the open arms of the O-maze were significantly greater (P< 0. 05) in the Light and Classical music groups. The hippocampal tissue of rats in the Light and Classical music group was relatively intact. The BDNF expression level in the hippocampus (P< 0. 01) and serum was significantly greater (P< 0.01) in the music groups. The CORT content in the hippocampus was significantly less in the music groups (P< 0. 01) and in the serum of only the Classical music group. The 5-HT content in the serum of the Light music group was greater (P< 0. 01) than the other groups. The content of IL-1β in the serum in both music groups was less than the Control group (P< 0. 01). Conclusions Light and classical music improve the behavior of depressed rats, indicating the potential value of music therapy in mental disease treatments.