This study was to explore the therapeutic effect and mechanism of the traditional Chinese medicine with the formula Da-Cheng-Qi-Tang (T-DCQT) and a modified Da-Cheng-Qi-Tang (M-DCQT) in a postoperative ileus (POI) mouse model. POI was induced via small bowel manipulation, and T-DCQT or M-DCQT was given by enema. The intestinal motility was measured with a charcoal mixture gavage. The intestinal tissues were collected for further studies by histopathological, qPCR, immunohistochemical staining, and Western blotting. Levels of inflammatory cytokines in blood were determined using a high-throughput liquid chip. We found that gastrointestinal dysfunction was alleviated after administration of either a T-DCQT or M-DCQT enema. Increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues of POI mice were reversed following treatment. IL-1α, IL-6, MIP-1β, and IL-17 levels were significantly reduced at 24 h and 48 h following treatment, while the MCP-1 level was only observed to be reduced at 24 h after the treatment. Furthermore, compared with the T-DCQT effect, M-DCQT treatment was more effective in alleviating the increased IL-6, MIP-1β, and IL-1α levels. So, we draw a conclusion that T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility in a POI mouse model.