Objectives Using the 5/6 nephrectomy rat as an animal model, we explored the capacity of creatinine and urea nitrogen removal of mutagenesis lactobacilli via gastrointestinal tract and its effect on renal pathology. Methods Sixty SD rats were randomly divided into 4 groups: sham group, model group, lactobacilli (LB) group, and mutagenesis lactobacilli (mut-LB) group. Rats were undergone 5/6 nephrectomy except the rats in sham group. Eight weeks after the surgery, 24h-urine, orbital blood and digestive juice were collected to determine creatinine (Cr) and urea nitrogen (UN) concentrations. Pathological changes of nephridial tissue were examined by HE and Masson staining. The expressions of TGF-β1 and FN in nephridial tissue were detected by immunohistochemistry. Results In mut-LB group, urinary Cr and UN levels had no significant changes (P＞0.05), serum and digestive Cr and UN levels decreased significantly (P＜0.01), renal tubular injury and renal interstitial fibrosis reduced significantly, and TGF-β1 and FN expressions decreased (P＜ 0.05), as compared with those in sham group and LB group. Conclusion Mutagenesis lactobacilli can decrease serum Cr and UN levels, reduce the expressions of TGF-β1 and FN in renal tissue, and alleviate renal interstitial injury and fibrosis, probably through the decomposition of small molecules in the gastrointestinal tract.