Objective To observe the immune regulation of embelin against systemic lupus erythematosus (SLE) in mice, so as to investigate its therapeutic effects on SLE and the possible mechanism. Methods The mouse model of SLE was established by intraperitoneal injection of 0.5 mL pristane, and urine protein level was detected to confirm the success of modeling. SLE mice then were randomly divided into control group and embelin group (n=5 for each group). The embelin group was given embelin 50 mg/kg by intragastric gavage, 100 μL/time, 3 times a week, while the control group was treated with 1% DMSO+PBS instead. After 1 month of administration, the lymph node size, spleen index and renal index of the mice were measured. The renal pathological changes were observed by HE staining; the serum concentrations of dsDNA, ssDNA and IgG were determined by ELISA; the Th cell subsets and B cell activation indexes were detected by flow cytometry. Results As compared with the control group, the embelin group had significantly reduced lymph node size, spleen index, kidney index, and mean glomerular area (P < 0.01), while elevated ratios of Th1/Th2 and Treg/Th17 (P < 0.05). As for the activation markers, the expression levels of CD69, CD86, MHC-Ⅱ in B cells and CD69, CD154 in Th cells were all obviously decreased (P < 0.05). In addition, embelin treatment remarkably lowered the concentrations of dsDNA, ssDNA and IgG in serum (P < 0.01). Conclusion Embelin plays a therapeutic role in SLE mice by regulating the balance of Th cell subsets and inhibiting the activation of Th and B cells.