The aim of this paper was to test lower, safe bexarotene dose administered alone and in combination with melatonin to improve its efficacy. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea in female Sprague-Dawley rats, administered in two doses intraperitoneally between 42.-54. postnatal days and chemoprevention was initiated 7 days prior to first N-methyl-N-nitrosourea injection and lasted 15 weeks. Bexarotene, particularly in combination with melatonin decreased mammary tumor incidence and frequency with a shift from poorly to well differentiated carcinomas. Bexarotene alleviated glycaemia and liver/heart muscle glycogen concentration decreased as well as liver/thymus malondialdehyde increased in comparison with control group. The combination of bexarotene and melatonin is therefore beneficial in preventive-curative model of experimental mammary carcinogenesis and may be applied in oncological practice as such.