This study was designed to investigate, the effect of Lactobacillus acidophilus the growth and pathogenicity of Proteus mirabilis. The inhibition activity of L. acidophilus against P. mirabilis bacteria was tested on solid and broth media (in vitro) in different incubation period (24, 48 and 72 hr),the result revealed 24 hr was the most efficient period of incubation for such purpose. Then the filtrate of Lactobacillus acidophilus was prepared and concentrated to three folds. It was found that the third fold was the most effective. Minimum inhibitory concentration (MIC) of L. acidophilus filtrate was determined after propagation of Lactobacillus acidophilus in MRS broth, results showed that the MIC of L. acidophilus was 60 % for P. mirabilis.On the other hand, In-vivo study was carried on forty mice, which were divided into eight groups, each group contains five animals to investigate the effect of P. mirabilis on different organs of these animals (liver, stomach, intestine and kidney). Histopathological examination showed that (1.5 x 108 cfu/ml) dose of P. mirabilis when administrated orally causes certain clinical pathological effect on liver, intestine and kidney tissue, and there were no histological change seen in stomach tissue, the effect was decreased when administrated orally with same dose of L. acidophilus. This result reflects the ability of L. acidophilus to reduce the certain clinical pathological changes in mice organs. Also the effect of P. mirabilis on the level of liver functional enzymes (GOT, GPT) in serum was determined. It's clear that there is a sign of increase in the level of both enzymes, and this level return with a normal range after treating the animal with L. acidophilus.