Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that is classified into 2 major forms, Crohn’s disease and ulcerative colitis. Abnormalities of intestinal innate immune functions have been regarded as key properties in immunogenetic profile of IBD. Intestinal macrophages have important roles in the regulation of immune homeostasis in the intestine. Recently, we have demonstrated that the enhancement of anti-inflammatory cytokine IL-10 production in the intestinal macrophages has a potential to be a novel therapeutic mechanism against IBD. Thus, to address the development of new therapeutic medicines for IBD, we have screened compounds derived from medicinal herbs for the ability to enhance IL-10 production in the intestinal macrophages. Firstly, we performed an in vitro screening of 96 compounds derived from medicinal herbs that are frequently used in Japan using bone marrow-derived macrophages (BMDMs). BMDMs were prepared from BALB/c mice and cultured with M-CSF (100 ng/ml) for 7 days. Then, compounds (10 μM) were added to BMDMs 1 hour before LPS stimulation (100ng/ml) for 24 hours. Among 96 samples, we found that 2 compounds significantly increased the IL-10 production in BMDMs. Next, we examined the effect of these 2 compounds in the IL-10 production of intestinal macrophages isolated from colonic lamina propria of mice. These 2 compounds also significantly increased the expression of IL-10 mRNA in the intestinal macrophages. Furthermore, these compounds did not affect mRNA expression of proinflammatory cytokines in the intestinal macrophages. The present results indicate that these compounds we found have therapeutic potential for IBD through the enhancement of IL-10 production in the intestinal macrophages.