Abstract: L.paracasei subp. paracasei M5-L inhibition of Shigella sonnei adhesion to HT-29 cells and the type of molecules in the M5-L cells surface which effecting the inhibition of S.sonnei were investigated. In exclusion, competition and displacement assays, L.paracasei subp. paracasei M5-L exhibited significant inhibitory activity (p <0.05) , preventing 55% , 33% and 30% of the S.sonnei cells from adhering to HT-29 cell respectively.Treatment with metaperiodate on the M5-L did not affect the inhibitory activity , which showed that the carbohydrates did not involved in the inhibition adherence. When the M5-L treated with 5mol/L LiCl , the inhibition activity was decreased significantly, which indicated the S-layer protein was the important molecules in the inhibition activity. In addition, the S -layer proteins exhibited strongly inhibitory effects on the S.sonnei adherence to HT-29 cells.