Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg(-1) body weight for three consecutive days before the ip injection of EAT cells (2×10(6)). Irinotecan was administered ip at dose of 50 mg kg(-1) on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.