Background: TiaochangXiaoliu decoction (TXD) has an anti-tumor effect in clinical practice. We further investigated the role of TXD in colorectal cancer (CRC). Methods: Mouse models of CRC were induced by azomethane (AOM)/dextran sulfate sodium (DSS), with sixty male C57BL/6 mice randomly divided into six groups (10 mice/group): a control group, AOM/ DSS group, TXD at low dose (L-dose) group, middle dose (M-dose) group, high dose (H-dose) group, and Celecoxib (Cel) group. The colorectum, serum, and plasma of mice in each group was collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to colorectal tissues, ELISA used for detecting INF-gamma, IL-2, and TNF-alpha expression in serum, and flow cytometry used for measuring the proportion of CD4+, CD8+, CD4+/CD8+, and NK cells in plasma. Results: Compared with the control group, the AOM/DSS group showed tumor masses in the colorectum and different degrees of pathological damage in the intestine. AOM/DSS induction also resulted in an increase in INF-gamma, IL-2, and TNF-alpha expression in serum, and a decrease in the percentages of CD4+, CD8+, CD4+/CD8+, and NK cells(P<0.05). In comparison with the AOM/DSS group, with the increase of TXD dose, the number of tumors decreased significantly, and intestinal structure and mucosal inflammatory cell infiltration also improved. Further, in comparison with the AOM/DSS group, all three doses of TXD and celecoxib caused an increase in the contents of CD4+, CD8+, CD4+/CD8+, and NK cells in plasma. In addition, in the M-dose, H-dose, and Cel groups, INF-gamma, IL-2, and TNF-alpha expression showed a marked decrease, and the reduction in these two groups treated with TXD was dose-dependent. Conclusions: TXD leads to a marked reduction in the number of tumors and inflammatory cell infiltration in CRC mice. This decoction significantly decreased the levels of INF-gamma, IL-2, and TNF-alpha in serum, and increased the contents of CD4+, CD8+, CD4+/CD8+, and NK cell in the plasma of mice with AOM/DSS-induced CRC.