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BACKGROUND:?Severe acute pancreatitis (SAP) can result in intestinal mucosal injury. This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP. METHODS:?Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared by the thin-film method. SAP models were prepared by a uniform injection of sodium taurocholate (2 mL/kg body weight) into the subcapsular space ofthepancreas.Sprague-Dawleyratswererandomlydividedinto a control group (C group), a SAP plus PBS-containing liposomes group(Pgroup)andaSAPplusclodronate-containingliposomes group (T group). At 2 and 6 hours after the establishment of SAP models, 2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-α and IL-12. Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining, while apoptosis was detected using TUNEL staining. In addition, the macrophage markers cluster of differentiation 68 (CD68) in the intestinaltissuewasassessedwithimmunohistochemistry. RESULTS:?At the two time points, the levels of TNF-α and IL-12 in the P group were higher than those in the C group (P