Propolis, the resinous hive product collected by bees, is important in the defense of the hive. The effects of propolis on growth and glucosyltransferase activity of Streptococcus sobrinus 6715, Streptococcus mutans PS14 and Streptococcus cricetus OMZ61 in vitro, and on dental caries in rats infected with S. sobrinus 6715 were investigated. Propolis had antimicrobial activity against S. sobrinus, S. mutans and S. cricetus, and inhibited both water-insoluble glucan synthesis and glucosyltransferase activity. In rats inoculated with S. sobrinus, about half of their fissures were carious, while dental caries was significantly less (p = 0.01) in rats given propolis. Dental caries was markedly decreased by the multiple actions of propolis which had antimicrobial activity, inhibited water-insoluble glucan synthesis, and inhibited glucosyltransferase activity. No toxic effects of propolis on the growth of rats were observed under experimental conditions in this study. These results suggest that propolis can control dental caries in the rat model system.