Background: We have demonstrated that outer membrane antigens of Haemophilus parainfluenzae (OMHP) are potentially involved in IgA nephropathy (IgAN). In this study, we established an experimental model of IgAN using OMHP antigens and investigated the nephritogenicity of OMHP antigens. Methods: One hundred and twenty C3H/HeN mice were administered OMHP antigens orally (PO group) or intraperitoneally (IP group). Mice were sacrificed at 10, 20, 30, 40, and 50 weeks of age to examine sequential glomerular changes and to measure levels of IgG, IgA, and IgM antibody against OMHP by ELISA. Results: Glomerular deposition of IgA and increases in the amount of mesangial matrix were observed in the PO group and the IP group from 40 and 30 weeks of age, respectively. Mice in both groups showed glomerular deposition of OMHP antigens from 30 or 40 weeks of age. Levels of IgA antibodies against OMHP were significantly increased in the PO and IP groups compared with controls. There was a significant correlation between mesangial proliferation and glomerular deposition of IgA. Conclusions: Administration of OMHP antigens to mice may induce glomerular deposition of IgA and mesangial proliferation, resembling the changes seen in IgAN, with increases in IgA antibodies against OMHP antigens. This is the first use of OMHP antigens to establish an active model of IgAN.