The objective of the present study was to determine the possible immune-enhancing effects of a substance extracted from a submerged culture of Lentinus edodes with rice bran (SLRB). According to the results obtained by measuring the in vitro macrophage activity of the exo-biopolymer from SLRB, it appears to exhibit activity similar to that of LPS, and this activity seems to occur in a dose-dependent manner. According to the results obtained by measuring splenocyte proliferation, the exo-biopolymer appears to induce an increase in proliferation of approximately 1.4-fold compared to the control group. We measured the proliferation of bone marrow cells in order to evaluate gut immunity and, according to our results, proliferation was increased to 109% that of the control group, and was similar to that associated with LPS. In order to characterize the enhancement of immunological activity in vivo, we orally administered the exo-biopolymer (25, 50, 250 mg/kg bw) to C3H/He mice, and then measured the macrophage activity, determining that the activity was higher than that of the controls at concentrations of 50 and 250 mg/kg. Therefore, the exo-biopolymer from SLRB can be considered to be a useful a BRM agent, as it clearly allows some protection against immunological diseases.