Objective：To investigate the possible reversal effects of 1,3-diphenyl-1,3-propanedione (DPPD) for cocaine-induced content changes of neurotransmitters of brain in mice. Methods: In this study, 36 healthy ICR male mice were randomly divided into control group, cocaine group, three DPPD pretreatment groups (200, 400, and 800 mg/kg) and DPPD alone group (800 mg/kg). The mice in control group were administered intragastrically with 1% Tween 80 for 3 d, and the mice in cocaine group were administered intragastrically with 1% Tween 80 for 2 d before cocaine was injected subcutaneously on the 3rd day. The mice in the three DPPD pretreatment groups were administered intragastrically (DPPD 200, 400, and 800 mg/kg) for 3 d before cocaine was injected subcutaneously 30 min after the administration on the 3rd day. The mice in DPPD alone group were administered intragastrically with DPPD at dose of 800 mg/kg for 3 d. The mice were sacrificed 20 minutes after cocaine injection. The contents of dopamine (DA) and 5-hydroxytryptamin (5-HT) in the mice brain were determined by high performance liquid chromatography (HPLC)-fluorescence detector, the contents of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in the mice brain were determined by HPLC-ultraviolet detector, and the neurotransmitter levels were compared between the groups.  Results: The results showed that as compared with the control group, DA and GABA contents in cocaine group increased significantly (P<0.01 and P<0.05), while Glu content decreased (P<0.05). As compared with cocaine group, the DA levels in the three DPPD pretreatment groups (200, 400, and 800 mg/kg) all decreased significantly (P<0.01). In DPPD 200 mg/kg pre-administration group, GABA content decreased (P<0.05), and the contents of the four kinds of neurotransmitters had no statistical differences with those of the control group. Conclusion: DPPD may have potential reversal effects of the content changes of neurotransmitters in mice brain induced by cocaine at a lower dose.