Seleno-polysaccharides possess a variety of biological activities. In the present study, we further investigated the immunomodulatory effects of low molecular-weight seleno-aminopolysaccharides (LSA) in intestinal porcine epithelial cells (IPEC-1), and the molecular mechanisms of these effects. Analysis by ELISAs revealed that LSA could significantly increase the secretion of nitric oxide (NO), interleukin- 6 (IL-6), interleukin- 10 (IL-10), and tumor necrosis factor alpha (TNF-α). Moreover, LSA dramatically increased the gene expression levels of TNF-α, IL-6, IL-10, and iNOS in IPEC-1 cells, as determined by qRT-PCR. Western blot analysis further determined that LSA promotes inhibitor kappa B α (IĸBα), nuclear factor- kappa B (NF-κB) p65 phosphorylation. Taken together, these findings suggested that LSA has immunomodulatory activity on IPEC-1 cells, and its mechanism may be related to activation of the NF-ĸB signaling pathway.