Immunoglobulin A nephropathy (IgAN) is associated with mucosal IgA defect. Probiotics regulate specific and innate immunity. We evaluated the effect of Saccharomyces boulardii on experimental IgAN in mice. Four groups of BALB/c mice (eight for each) were formed. Group 1 was immunized by oral poliovirus vaccine (OPV) at 0, 14, and 28 days. Group 2 was also given S. boulardii in addition to OPV. Group 3 was given only S. boulardii, whereas group 4 received no treatment. At week 6, after urine and serum samples were obtained for urinalysis and serum creatinine and IgA measurements, all animals were sacrificed to get their kidneys for histopathological evaluation. Urinalysis and serum creatinine levels were normal in all groups. Serum IgA level was increased only in group 1. Whereas group 1 had mesangial proliferation, histology was normal in the other groups. Predominant IgA deposition was universal in group 1, whereas it was either not present or minimal in other groups. Three mice in group 1 also had C3 deposition, which was absent in other groups. Electron microscopy revealed mesangial proliferation, matrix expansion, focal glomerular basement membrane thickening and electron-dense deposits in group 1 only, whereas the other groups were normal. In conclusion, enteral S. boulardii prevented OPV-induced IgAN in mice.