Inbred strains of mice and rats are widely used in preclinical investigations evaluating the effectiveness of glycan-based biomecines, however, the glycan specificity repertoires of serum Abs in rodents have not been fully characterized. In the present study, serum antibodies in naïve mice and rats of different inbred strains were analyzed for specificity against 4 representative carbohydrate structures including PGA (1,4-linked alpha-D-galactopyranosyluronic acids), beta-glucan, mannan and alpha-glucan (dextran). Mannan was not recognized by serum Abs from any of the mouse and rat strains. Serum IgM in naïve F344, BN and Lewis rats recognized PGA and beta-glucan and, less strongly, dextran. High titer circulating IgM against PGA were found in mice of BALB/c, C57BL/6, C3H/NeH and BXSB strains. C3H/NeH was the only strain which also produced low titer IgM against beta-glucan and dextran. Age-related production of high titer IgM, IgA and IgG Abs against alpha-glucan was observed in BXSB mice. Intraperitoneal immunization of BALB/c and C57BL/6 mice with beta-glucan elicited strong IgM responses, while immunization with PGA also led to an increase of anti-PGA IgM Ab titers. These results provide useful information on the characteristics of glycan-specific natural antibody repertoires in rodents.