The objective of this study was to evaluate the modulatory effects of Lactobacillus reuteri ZJ617 and ZJ615, which have high and low adhesive abilities, respectively, and Lactobacillus rhamnosus GG (LGG) on immune responses and metabolism in mice stimulated with lipopolysaccharide (LPS). Six C57BL/6 mice per group were orally inoculated with ZJ617, ZJ615 or LGG for one week (1 × 10(8) CFU/mouse) and i.p. injected with LPS (10 mg/kg) for 24 h. Compared with the LPS stimulation group, ZJ615, ZJ617 and LGG significantly decreased TNF-α levels in the sera of mice stimulated by LPS. ZJ615 and LGG significantly down-regulated mRNA levels of cytokines and Toll-like receptors, and suppressed activation of MAPK and NF-κB signaling, while ZJ617 up-regulated anti-inflammatory cytokine IL-10 mRNA levels in the ilea of mice stimulated by LPS. Correlation analysis confirmed that adhesive ability is relative with the immunomodulation in the ilea of mice. There were 24, 7 and 10 metabolites and 10, 9 and 8 major metabolic pathways with significant differences (VIP > 1, P < 0.05) between the LPS and ZJ617 + LPS groups, the LPS and ZJ615 + LPS groups, and the ZJ617 + LPS and ZJ615 + LPS groups, respectively. The results indicated that both ZJ617 and ZJ615 could modulate the intestinal immune responses and metabolism in LPS-stimulated mice.