Many natural resources obtained from plants have been studied for their utility as host defense potentiators. In the present study, we investigated whether a glycoprotein fraction from rice (Oryza sativa) bran (GFRB) could modulate immune responses such as the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the RAW 264.7 macrophage cell line. GFRB, which contained 65.7% of protein and 7.7% of total sugar, was prepared by treating an aqueous extract of rice bran with 80% (NH4)2SO4 and the extraction yield was 4.9%. GFRB consisted of 5 bands with varying molecular weights by SDS-PAGE and remarkably improved production of NO in RAW 264.7 murine macrophage cells, up to approximately 10-fold compared to the normal control at 100μg/mL concentration. In RAW 264.7 cells treated with 50μg/mL GFRB, released levels of various cytokines such as TNF-α, IL-1β, IL-6, and IL-10 were 2824.4±90.7, 224.5±4.0, 524.3±4.8, and 143.0±9.5pg/mL, respectively, which were higher than the levels in normal controls. Moreover, GFRB exhibited no cytotoxicity. According to the results of region-selective enzyme hydrolysis, the immune responses against GFRB were elicited by the glycans in the GFRB. These results show the potential of GFRB as a functional therapeutic agent with demonstrable immunostimulatory activity.