Giardia lamblia is considered one of the most common intestinal parasites that infect human. It is the causative agent of giardiasis, a major cause of diarrheal illness. Current recommended treatment usually accomplished using one of several drugs. However, resistance is increasing, and new alternatives are being sought. Currently the interest in alternative biotherapeutic strategies which have included natural interventions such as probiotic Lactobacillus bacteria which displays antiprotozoal effect is required. The present study was conducted on 57 laboratory bred Swiss albino mice provided by animal house in Theodor Bilharz Research Institute to evaluate the effect of Lactobacillus casei on Giardia lamblia versus the commercially used drug metronidazole in experimentally infected mice. The mice were divided into two main groups: group (A) which included normal non infected mice and group (B) which included infected mice. Each group was subsequently divided into 4 subgroups (control, treated with metronidazole, treated with L. casei and treated with both metronidazole & L. casei) in addition to prophylactic subgroup in group (B) (received L.casei seven days before and 10 days after infection directly then for ten days after approval of infection by Giardia cysts). The mice were infected with Giardia cysts in a dose of 10⁴±10 cysts/mouse. Parasitological, histopathological and immunohistochemical assessments of the drug effect were done. The obtained results of infected treated group were plotted in comparison to healthy control, non-infected treated mice and infected control. Parasitological assessment was done through counting of cysts output of infected mice 7 and 10 days after starting treatment. Histopathological and immunohistochemical assessments were done by examining sections of the duodenum. There was a significant reduction of the excreted cysts count in infected treated subgroups. The highest cyst reduction was in prophylactic and treated with both L.casei & metronidazole subgroups compared to metronidazole treated and infected control.  Histopathological examination of infected control revealed profound effect on the structure of the intestinal mucosa with diffuse loss of brush border of intestinal villi. After treatment there was remarkable improvement of these histopathological findings especially in prophylactic subgroup compared to metronidazole treated and infected control. Immunohistochemical staining revealed marked increase in IgA secretory plasma cells in prophylactic and treated with both L.casei & metronidazole subgroups compared to infected control and metronidazole treated mice. The results achieved that probiotics have a promise in the treatment of giardiasis. The protective response of probiotic in mice is better when Lactobacilli were administered for many days before infection.