Severe burn injury and cirrhosis often cause the translocation of bacterial endotoxins into blood, leading to systemic damage and even death. Our previous studies have shown that anti‐lipopolysaccharide egg yolk antibody (anti‐LPS IgY) can neutralize bacterial endotoxins
in vitro
and
in vivo
effectively, thereby reducing endotoxin damage. Whether anti‐LPS IgY can be absorbed into the blood through the intestinal barrier and neutralize endotoxins in circulation remains unclear. In this study, we used
in vivo
small animal imaging techniques, protein purification, molecular biology, and mass spectrometry to show that intragastrically administered anti‐LPS IgY is detected in the blood of mice as an intact molecule and has the capacity to bind to LPS. Immunohistochemical analysis confirmed that anti‐LPS IgY is associated with the intestinal mucosa of mice. However, the route of absorption of this large protein molecule was not determined. This study suggests that anti‐LPS IgY can be absorbed into the circulation, with the same molecular mass as purified anti‐LPS IgY as a macromolecular protein, suggesting a new strategy for the prevention of damage caused by endotoxins.