Objective To investigate the risk of lymph node metastasis(LNM)in colorectal cancer(CRC)based on the M2 macrophage activity biomarker soluble CD 163(sCD163).Methods The clinical data and preoperative blood samples of 152 patients with CRC and 58 patients with colorectal adenoma who received primary surgery in Jingmen Central Hospital from January 2018 to May 2019 were collected.Blood samples were collected the day before surgery,and enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of sCD163,carcinoembryonic antigen(CEA),and carbohydrate antigen 199(CA199).Postoperative follow-up was conducted with a cutoff date of April 30,2024,and the overall survival and disease-free survival were recorded.Results The level of sCD163 in patients without LNM was significantly lower than in those with LNM[(2.79±0.76)mg/L vs(4.25±1.50)mg/L,t=7.958,P<0.01].Multivariate logistic regression analysis indicated that sCD163>3.50 mg/L was an independent risk factor for LNM in CRC patients(HR=13.973,95%CI:5.385-36.259,P<0.05).sCD163>3.50 mg/L had the highest ability to predict lymph node metastasis in CRC patients(AUC=0.742),with a sensitivity of 68.8%and a specificity of 79.7%.There were 35 patients(46.1%)died in the group of sCD163>3.50 mg/L,and 12 patients(15.8%)died in the group of sCD163≤3.50 mg/L.There was a significant difference in overall survival between the two groups(log-rank x2=15.583,P<0.01).There were 42 patients(55.3%)in the group of sCD163>3.50 mg/L relapsed,and 25 patients(32.9%)in the group of sCD163≤3.50 mg/L relapsed.The difference in recurrence-free survival between the two groups was statistically significant(log-rank x2=8.368,P=0.004).Conclusion Elevated levels of the biomarker sCD163,which reflects M2 macrophage activity in tissues,are significantly associated with LNM and poor prognosis in CRC patients,and sCD163 may be a potential predictive factor for identifying CRC patients at high risk of LNM.