Abstract: The juvenile grass carps (Ctenopharyngodon idellus) with an average body mass of (6.0±1.5) g were selected to test the acute toxic effect of lead (Pb). The LC₅₀ value of the semi-lethal concentration corresponding to 96 h was obtained and the safe concentration (SC) of Pb on grass carp juveniles was calculated. The changes of intestinal tissue structure, Pb concentration, digestive enzyme activity and the expression of inflammation and intestinal structure-related genes were detected at 0, 3, 6, 12, 24, 48, 72 and 96 h after stress. The result showed that the SC of Pb on juvenile grass carps for 96 h was 3.46 mg/L. Pb was enriched in the intestines of grass carp after challenge. The expression levels of inflammation-related genes, IL-1β, TNF-α and IL-10, were significantly up-regulated upon lead stress. The activity of trypsin and lipase showed significant down-regulation at the late stage of the experiment. The transcriptional levels of the gene of intestinal tight junction proteins, Claudin-3 and ZO-1, significantly up-regulated after lead challenge. The depth of the crypt and the thickness of the intestinal wall increased and then gradually recovered. After the enrichment of Pb in the intestine, the structural changes of the intestine are coordinated with functional changes. This study will provide a test basis for better understanding of the toxic mechanism of Pb on freshwater aquaculture, and provide data support to ensure the quality of aquatic products and protect fishery resources.