Objective: The study aimed to investigate the alleviating effect and mechanism of Sparassis latifolia polysaccharides (HSCPs) on intestinal barrier damage in lead-exposed mice under cohousing conditions. Methods: Sixty Kunming mice were randomly divided into blank control group (NC)， Pb group (Pb)， HSCPs group， co-housing group between Pb group and HSCPs group (CO Pb+CO HSCPs). After 8 weeks of feeding， the concentrations of red blood cells and hemoglobin were measured by an automatic blood cell analyzer. ICP-MS was used to determine the Pb content in the blood， small intestine， and feces of mice. The content of lipopolysaccharides in serum， and levels of small intestine lysozyme， β-defensin and sIgA were detected by ELISA kit. HE staining and AP-PAS was used to observe the microstructure and the number of goblet cells in the small intestine. qPCR was used to measure the mRNA expression levels of ZO-1， ZO-2， Occludin， Claudin-1， Lyz， and Ang4 in the small intestine； intestinal flora was analyzed by 16S rRNA amplicon sequencing. Endogenous metabolites in serum were explored by metabolomics analysis. Results: Compared with the NC group， the Pb group showed a significant increase in levels of blood Pb， small intestine Pb， fecal Pb and serum lipopolysaccharide， and relative abundance of Desulfovibrio (P < 0.05). The number of red blood cells， hemoglobin concentration， levels of lysozyme， β-defensin and sIgA， mRNA levels of ZO-1， ZO-2， Occludin， Claudin-1， Lyz and Ang4， and the relative abundance of Lachnospiraceae_NK4A136_group， Alloprevotella and Faecalibaculum significantly decreased (P < 0.05). The villi of the small intestine became shorter， broken and partly falling， the space between villi increased， and the goblet cells decreased significantly. Compared with the Pb group， the levels of blood Pb， small intestinal Pb， and the relative abundance of Desulfovibrio significantly decreased (P < 0.05)， while the numbers of red blood cells， hemoglobin concentration and the relative abundance of Faecalibaculum increased significantly in the CO-Pb group (P < 0.05). In addition， the levels of lysozyme， β-defensin and sIgA， and mRNA expression levels of ZO-1， ZO-2， Occludin， Claudin-1， Lyz， and Ang4 were not significantly affected. The villi of the small intestine were short and broken， goblet cell were less. The contents of serum lipopolysaccharides， blood Pb， and small intestinal lead， and the relative abundance of Desulfovibrio in the HSCPs and CO-HSCPs groups significantly decreased (P < 0.05)， while hemoglobin concentration， fecal Pb content， levels of lysozyme， β-defensin， and sIgA content， the expression levels of ZO-1， ZO-2， Occludin， Claudin-1， Lyz， and Ang4， and the relative abundance of Alloprevotella increased significantly (P < 0.05). There were 14 different metabolites in the co-housing mice involved in seven metabolic pathways including glycerol phospholipid pathway， arachidonic acid pathway and linoleic acid pathway. Conclusion: Co-housing could improve the damage of intestinal barrier in Pb-induced mice by transfecting the intestinal flora in the CO-HSCPs mice to the CO-Pb mice， thus increasing the relative abundance of beneficial bacteria in the CO-Pb group and affecting seven metabolic pathways， including glycerol phospholipid pathway， arachidonic acid pathway， linoleic acid pathway， and so on.