Objective:To explore the peripheral blood levels changes of soluble glycosylation end product receptor (sRAGE), endotoxin and Toll-like receptor (TLR) in patients with severe acute pancreatitis (SAP) complicated with peritoneal cavity infection, and clarify the relationship between indexes and pathogenetic condition.Methods:The clinical data of 105 patients with SAP in Shanghai Pudong New Area People′s Hospital from January 2017 to December 2020 were retrospectively analyzed. Among them, 28 cases had peritoneal cavity infection (infection group), and 77 cases had peritoneal cavity infection symptoms but undiagnosed (non-infection group). The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) at admission was recorded. When patients had the suspected symptoms and signs of peritoneal cavity infection, the serum levels of sRAGE, endotoxin, TLR4 and TLR9 were detected by enzyme-linked immunosorbent assay. The correlation between serum levels of sRAGE, endotoxin, TLR-4, TLR-9 and APACHE Ⅱ was analyzed by Pearson analysis; the risk factors of peritoneal cavity infection in SAP patients were analyzed by multivariate Logistic regression; the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of serum sRAGE, endotoxin, TLR-4 and TLR-9 in peritoneal cavity infection were evaluated in patients with SAP; the Kaplan-Meier survival curve was drawn, and the comparison used log-rank test.Results:The serum sRAGE, endotoxin, TLR-4 and TLR-9 in infection group were significantly higher than those in non-infection group: (822.16 ± 104.51) ng/L vs. (728.09 ± 96.47) ng/L, (62.59 ± 20.11) ng/L vs. (41.62 ± 13.64) ng/L, (45.17 ± 8.54) μg/L vs. (37.34 ± 6.22) μg/L, (26.35 ± 6.73) μg/L vs. (20.02 ± 5.49) μg/L, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that the serum sRAGE, endotoxin, TLR-4 and TLR-9 were positively correlated with APACHE Ⅱ in patients with SAP ( r = 0.632, 0.556, 0.521 and 0.631; P<0.05). Multivariate Logistic regression analysis result showed that the combined organ function damage, shock, hypoxemia and serum sRAGE, endotoxin, TLR-4 and TLR-9 were independent risk factors of peritoneal cavity infection in patients with SAP ( P<0.05). ROC curve analysis result showed that the area under the curve for the serum sRAGE, endotoxin, TLR-4 and TLR-9 combined diagnosis of peritoneal cavity infection in patients with SAP was the largest, which was 0.910 (95% CI 0.838 to 0.957, P<0.01), with a sensitivity of 82.14% and a specificity of 87.01%. According to the ROC curve cut-off value of serum sRAGE, endotoxin, TLR-4 and TLR-9 (764.58 ng/L, 58.01 ng/L, 40.24 μg/L and 22.61 μg/L), the 28 patients with SAP complicated with peritoneal cavity infection were divided into high levels patients (21, 14, 23 and 22 cases) and low levels patients (7, 14, 5 and 6 cases); Kaplan-Meier survival curve analysis result showed that the 28-day survival rates in patients with high levels of sRAGE, endotoxin, TLR-4 and TLR-9 were significantly lower than those in patients with low levels (61.90% vs. 71.43%, 50.00% vs. 78.57%, 60.87% vs. 80.00% and 59.09% vs. 83.33%), and there were statistical differences ( P<0.05). Conclusions:The serum sRAGE, endotoxin, TLR-4 and TLR-9 have a high combined diagnostic value in SAP complicated with peritoneal cavity infection, and they are all related to the severity of the disease and have a significant impact on survival.