This study was designed to evaluate the ability of Saccharomyce buolardi as effective probiotic against Shiegella flexneri. Mice treated with S. boulardii and infected with Sh. flexneri, then serum levels of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) of treated mice were measured and histological sections were made from liver to evaluate protective effect. Results showed that mice treated with S. boulardii exhibited no significant p≤0.05 differences in serum level of AST and ALT 131,67 respectively U/L in comparison with their levels in serum of control group 113.2, 72.86 U/L. Mice infected with Sh. flexneri showed a significant increase in serum level of AST and ALT 198, 101 U/L in comparison with their levels 113,72 U/L in control group. Mice treated with S. boulardii and infected with Sh. flexneri showed a significant decrease in serum level of AST and ALT in comparison with their levels in mice infected with Sh. flexneri 80.13,78.26 U/L vs. 198 and 101 U/L respectively. Histopathological study showed that infection with Sh. flexneri caused a necrosis, degenerative changes and inflammatory cells infiltration as compared with control, while treatment with S. boulardii prevented the histopathological effect of Sh. flexneri.