The effect of oral administration of Hochuekkito (HET; Bu-Zhong-Yi-Qi-Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen-specific antibodies in mucosal site, ovalbumin (OVA)-entrapped biodegradable microparticles (OVA-microparticles) were used as an antigen. Mice were orally immunized with OVA-microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA-specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payer's patches were investigated for cytokines production, it was found that the IFN-γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyer's patch cells revealed enhanced expression of L-selectin gene. The increase of L-selectin positive cells in B lymphocytes fraction was observed in Peyer's patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN-γ secretion and increased population of L-selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine.