ABSTRACT Tumors and tumor-bearing hosts exhibit markedly altered circadian rhythms, which serve as markers in the early diagnosis and prognosis of cancer. Our study presents the effect of melatonin on circadian rhythms of lipid peroxides and antioxidants in N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. The circadian rhythm characteristics (acrophase, amplitude, and mesor) of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) were markedly altered in NDEA-treated rats. Melatonin administration caused a significant increase in the amplitude and mesor values of antioxidants and a significant decrease in the mesor values of TBARS. Further delays in acrophase in NDEA-treated rats were reversed by melatonin administration. In conclusion, melatonin may exert its chemopreventive effect by its role as an antioxidant as well as by altering the circadian rhythm characteristics.