It has been demonstrated that cadmium (Cd) is carcinogenic to rodent prostate. However, the mechanism of its toxicity is far from fully understood. In the present study, the effects of oral Cd exposure (0, 50, 100, 200 ppm in drinking water) on serum sex hormone levels, the expression of MT-I and MT-II mRNA, and the zinc content of rat prostate were assessed. With Cd administration, serum testosterone (T) levels significantly increased in all Cd groups after 3 months and in the 200 ppm Cd group after 6 months. A significant depression in the serum luteinizing hormone (LH) level was seen in the Cd group (200 ppm) after 6 months. It was noted that Cd administration resulted in a significant down-regulation in the expression of MT-I and MT-II mRNA in the rat ventral prostate. However, no Cd-induced changes in the mRNA expression of Metallothioneins (MTs) were detected in the dorsolateral prostate. After Cd administration, the content of Cd in both the ventral and dorsolateral lobes of the prostate significantly increased with increasing dose and duration of Cd administration. In contrast, the Zn content decreased with Cd administration in both the ventral and dorsolateral lobes of the rat prostate. Taken together, these results suggest that oral Cd exposure may disrupt endocrine homeostasis, changing the distribution of Zn and the mRNA expression of MTs in rat prostate, and that such Cd-induced changes may contribute to the susceptibility of prostate to the carcinogenicity of this heavy metal.