This study was aimed to investigate the protective effect of some probiotic microorganisms in mice infected with Salmonella typhimurium. A total of (119) samples including food, stool, and vaginal swabs were collected from various regions of Baghdad city. Lactobacillus spp. and Saccharomyces spp. Were isolated from the samples to be used as probiotics. Twenty isolates of Lactobacillus spp., 17 of Saccharomyces cerevisiae and one isolate of Saccharomyces boulardii were obtained from the samples. Nine isolates of Lactobacillus and eight of Saccharomyces isolates were found to possess inhibitory effect against S. typhimurium )in vitro(. The most efficient isolate of each of Lactobacillus (Lb. acidophilus Gb9) and Saccharomyces (S. cerevisiae Fs28) were selected to evaluate their effects on the immunological (total and absolute count of leucocytes, phagocytic index, and total immunoglobulin level) and histopathological (intestine, liver, and spleen) aspects of albino male mice infected with S. typhimurium. For this purpose, 35 mice were divided into 7 groups before subjection to various treatments. Results obtained could be summarized as follows: 1. Lb. acidophilus Gb9 and S. cerevisiae Fs28 were found to be the most efficient probiotic isolates against S. typhimurium (in vitro). 2. The 3-fold concentrated filtrates of both isolates resulted in the highest inhibitory effect against the pathogenic bacteria (in vitro) as compared with the unconcentrated, 1-fold, and 2-fold concentrated filtrates. 3. The total counts of leukocytes of mice infected with S. typhimurium were significantly increased after treatment with Lb. acidophilus Gb9 and S. cerevisiae Fs28 cells. 4. Lb. acidophilus Gb9 cells led to increase the total counts of lymphocytes, neutrophils, and monocytes in mice infected with S. typhimurium. 5. No significant differences were detected in the total counts of eosinophil and basophile among the treated groups. 6. Treatment of mice with probiotics cells, especially Lb. acidophilus Gb9, S. cerevisiae Fs28, and the (1:1) mixture of both isolates caused significant decreases in the phagocytic indexes of mice infected with S. typhimurium. 7. Highest gamma-globulins levels were obtained in mice treated with Lb. acidophilus Gb9 cells then infected with S. typhimurium. 8. The cells and filtrates of Lb. acidophilus Gb9 and S. cerevisiae Fs28 led to alleviate the cytotoxic effects of S. typhimurium on intestines, liver, and spleen of mice