Lactobacillus delbrueckii (LAB) has been demonstrated to exert versatile beneficial effects on modulating intestinal immunity, increasing gut microbial diversity, promoting growth performance, and even preventing disease onset in pigs. However, the underlying mechanism of LAB-mediated gut immunity regulation in piglets remains unclear. In this study, we found that supplementation of LAB significantly increases serum TNF-α, ileum IL-4, and IL-10 levels compared with the control group. Meanwhile, oral supplementation of LAB-modified gut microbial communities was evidenced by the increased abundance of the Lactobacillus genus in the colon. Mechanistically, LAB induced dendritic cell (DC) maturation and activation, which may be relevant to the activation of NF-κB and MAPK signaling pathways. Moreover, we found that oral administration of LAB during the suckling period shows long-lasting immunomodulatory impacts on intestinal immunity after weaning. Collectively, this study uncovers the mechanism of LAB in regulating the intestinal immunity of piglets, suggesting that LAB can be developed as an immunoenhancing biological agent during the suckling period.