Objective To investigate the regulatory effect of Auricularia auricular protein-polysaccharide complex (PPC) on lead (Pb) excretion in mice under co-cage rearing.Methods Sixty Kunming mice were randomized into blank control (NC), model (Pb), PPC, Co-Pb, and Co-PPC groups. After 8 weeks of feeding, the concentrations of red blood cells and hemoglobin are measured by a fully automated hematology analyzer. ICP-MS is employed to determine the Pb content in the whole blood, small intestine, and feces of mice. The ELISA kit is used to measure the content of lipopolysaccharides (LPS) in the serum and the levels of lysozymes, β-defensins, and sIgA in the small intestine.Results Compared with the NC group, the Pb group has increased levels of Pb in the blood, small intestine, and feces and LPS in the serum (P<0.05) and decreased red blood cell count, hemoglobin concentration, and levels of lysozymes, β-defensins, and sIgA (P<0.05). Compared with the Pb group, the Co-Pb group shows decreases in Pb content in the blood and small intestine (P<0.05), increases in the hemoglobin concentration and fecal Pb content (P<0.05), and insignificant increases in red blood cell count and levels of lysozymes, β-defensins, and sIgA. The PPC and Co-PPC groups show declines in the levels of LPS in the serum and Pb in the blood and small intestine (P<0.05), elevations in the hemoglobin concentration, fecal Pb content, and levels of lysozymes, β-defensins, and sIgA (P<0.05), and no significant difference in red blood cell count.Conclusion PPC can promote Pb excretion and improve blood and small intestine conditions in mice.