Abstract: Objective To investigate the therapeutic effect of Jiawei Huangqin (JWHQ) decoction on ulcerative colitis (UC) and the regulation of STAT3/NF-kB/IL-6 pathway. Methods Forty-eight mice were randomized into blank control group, model group, positive control (Sulfasalazine) group, and low-, moderate- and high-dose JWHQ Decoction groups (n=8). In all but the blank control groups, the mice were given 3% DSS in drinking water to induce UC, followed 7 days later by treatment with saline (blank control and model groups) or JWHQ Decoction by gavage (10 mL/k) for 7 consecutive days. After the treatment, the mice were euthanized and the colon length was measured and the histopathological changes were observed with HE staining. The expression levels of STAT3, NF-κB, and IL-6 in the colon tissues were detected with RT-qPCR and Western blotting. Results Compared with those in the blank control group, the colon length was significantly shortened and the pathological score of the colon tissue was significantly higher in all the other 5 groups (P<0.05). Compared with those in the model group, the colon length was significantly longer and the pathological scores were obviously reduced in all the 4 treatment groups (P<0.05). JWHQ Decoction at the high dose produced significantly better therapeutic effects than the positive drug in terms of the colon length (P<0.05) and the colon histopathological score (P<0.05); high-dose JWHQ Decoction also showed better effect than the other two doses (P<0.05), whose effects were comparable (P>0.05). The mouse models of UC showed significantly increased expression levels of STAT3, NF-κB, and IL-6 in the colon tissue (P<0.01), which were obviously lowered by the positive drug and JWHQ Decoction (P<0.01), especially at the high dose (P<0.01). JWHQ Decoction at the moderate dose produced similar effects with the positive drug on STAT3, NF-kB and IL-6 levels (P>0.05), and their effects were stronger than those of low-dose JWHQ Decoction (P<0.05). Conclusion JWHQ Decoction can improve UC in mice possibly by down-regulating the expression of STAT3, NF-kB and IL-6 in colonic tissue to affect the STAT3/NF-kB/IL-6 pathway.