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Background Active MMP-9 disruption of the extracellular matrix plays an important role in inflammatory disorders. In this study, we investigated the inflammatory role of MMP-9 and the extracellular matrix (ECM) breakdown product hyaluronan as a trigger for the postoperative intestinal inflammatory response of postoperative ileus. Methods A standardized intestinal surgical manipulation (SM) was performed on rats to produce ileus assessed by the oral non-digestible FITC-dextran transit assay. Isolated intestinal muscularis extracts were studied for mRNA expressions of IL-6, MMP-9 and CD44. Peritoneal MMP-9 activity was quantified using zymography. Peritoneal fluid and serum were quantified for hyaluronan and TIMP-1 levels by ELISA. Peritoneal macrophages were cultured and exposed to peritoneal fluid or synthetic hyaluronan for ELISA analysis of IL-6 and MIP-1α. Results Transit was significantly delayed after SM and extracts of the isolated jejunal and colonic muscularis demonstrated a significant induction of IL-6, MMP-9 and CD44 mRNAs compared to controls. Zymography confirmed significant MMP-9 activity in peritoneal fluid compared to controls. ELISA measurements showed a significant upregulation in hyaluronan and TIMP-1 in the peritoneal fluid and serum. Additionally, ELISA and RT-PCR measurements of peritoneal macrophages stimulated with postsurgical peritoneal fluid and synthetic hyaluronan resulted in higher expressions of IL-6 and MIP-1α in the macrophage supernatant. Conclusions Our results confirm that MMP-9 disruption in the ECM with hyaluronan release and muscularis CD44 receptor induction has the potential to trigger muscularis proinflammatory cascades which cause postoperative ileus and we suggest that MMP-9 inhibition may be a novel therapeutic approach to limit postoperative ileus.

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