Abstract: In order to explore the effect and its mechanism of paeoniflorin on PD-L1, a PD-L1 high expression cell model was established in interferon gamma(IFN-γ)-induced HepG2 cells. The cytotoxicity of paeoniflorin was detected by MTT assay. Flow cytometry, ELISA and RT-PCR were performed to detect protein and mRNA levels of PD-L1 regulated by paeoniflorin. In HepG2 cells and Jurkat T cell co-culture system, the expression of IL-2 was detected by ELISA. Besides, T cell proliferation was evaluated by CCK-8 method, and the protein expression levels of PD-L1, JAK and STAT3 after drug treatment were determined by Western blot. These results indicated that paeoniflorin could significantly down-regulate the levels of PD-L1 protein and mRNA. In addition, it increased the number of T cells and the concentration of IL-2 in the co-culture system. Furthermore, paeoniflorin could significantly inhibit the protein expression of JAK and STAT3. Au the above experimental data indicated that paeoniflorin could down-regulate the expression of PD-L1, and its mechanism might be related to the JAK/STAT3 pathway.