ABSTRACT Two studies were conducted to investigate the effects of dietary lysozyme on immune response, fecal microflora in sows and their offspring fed lysozyme from late gestation to the onset of lactation, and growth performance in weaned piglets. Four antibiotic-based treatments (chlortetracycline, colistin, and lysozyme) were applied in experiment 1. Lysozyme addition significantly increased final body weight, average daily gain, and average daily feed intake, improved feed:gain ratio (F:G), and decreased diarrhea rate in weaned piglets. In experiment 2, postpartum sows were fed diets either with amoxicillin and cephalosporin (SC) or lysozyme (SE). Piglets from SC sows were administered enrofloxacin and those from SE sows were administered lysozyme. Lysozyme treatment decreased serum IL-1, IL-6, and IL-10, but did not influence IL-8, TNF-α, or IFN-γ in weaned piglets. Sequencing revealed that lysozyme significantly decreased Chao-1 index in sows and weaned piglets, increased Bifidobacterium longum in sows, and Lactobacillus coleohominis, L. mucosae, L. amylovorus, and L. hamsteri in weaned piglets. The results suggest that dietary supplementation of lysozyme improved the growth performance of weaned piglets, and dietary supplementation of lysozyme for sows increased immune function and modulated the intestinal flora structure in sows and their offspring.