This study describes the in vivo activity of Lactobacillus acidophilus in Giardia lamblia infected BALB/c mice. Experimentally, it was observed that daily administration of lactobacilli 7 days before or in simultaneous inoculation with Giardia trophozoites efficiently reduced G. lamblia infection in mice. More specifically, excretion of Giardia cysts were reduced significantly in probiotic-treated groups, and resolution of infection was observed by day 21 post-inoculation. It was also observed that the lactobacillus count increased tremendously and continuously in faeces of all probiotic-fed mice, and was significantly higher as compared with that in control mice. Histological analysis of microvilli membrane integrity revealed that probiotic administration also protected mice against parasite-induced mucosal damage, whereas Giardia-infected mice had severe villous atrophy, oedema, vacuolation and ileitis. Immunologically, the anti-Giardia serum IgG level was not stimulated significantly by probiotic treatment administered both prior to and simultaneous with Giardia infection, but remained high after the infection peak. Taken together, the data demonstrates the anti-giardial effect of the probiotic in vivo by modulation of the intestinal epithelial cells, inhibiting the colonization of Giardia trophozoites and thereby reducing the severity of Giardia infection.