Rhinacanthus nasutus Kurz, a Thai medicinal plant which possess antiproliferative and pro-apoptotic effects on human cancer cells, was examined for chemopreventive potential against colonic neoplasms induced by azoxymethane (AOM) combined with dextran sodium sulfate (DSS) in mice. Male ICR mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) followed by 2% DSS in their drinking water for a week. Water extract of the roots of R. nasutus (RNR) was given to the animals intragastrically daily in the initiation and promotion phases. The one hundred mice were divided into 8 groups, one group treated with AOM plus DSS serving as a control. Four other groups received AOM/DSS and RNR at 100 or 500 mg/kg body weight for 5 weeks (initiation phase study) and for 14 weeks (promotion phase study). Another two groups were given RNR alone at 100 and 500 mg/kg body weight and the last group was maintained untreated. At the end of the study, we found that the incidence and multiplicity of colonic tumors in mice fed with RNR both at 100 and 500 mg/kg body weight in initiation phase were higher than those in the control group. Moreover, RNR feeding during the promotion phase also gave similar results. Our results suggest that water extract of the roots of R. nasutus Kurz. has no preventive potential against colon carcinogenesis induced by AOM/DSS in mice, rather increasing the incidence of colonic tumors when given during initiation and promotion phases. Further study on RNR should provide more information on mechanisms of its tumor promotion activity.