Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that has been demonstrated to induce alterations in reproductive organs while melatonin (ML), an antioxidant, present in plants and animals, is capable of protecting against EDC-induced alterations. Adult male Wistar rats (average weight, 240 + 10 g) were divided into four groups of ten animals each: Rats in group I (control) received oral 0.2 ml 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group II received intra-peritoneal 10 mg/kg BW/day ML. Group III received oral BPA dissolved in DMSO and solubilized in canola oil at 10 mg/kg BW/day. Group IV were treated with same dose of BPA as group III with a concomitant intra-peritoneal 10 mg/kg BW/day ML. All treatments lasted for 14 days. BPA significantly increased the prostatic index of the rats while ML ameliorated it. BPA significantly increased serum levels of estrogen as well as prostate-specific antigen but decreased serum testosterone in the rats while concomitant treatment with ML ameliorated these alterations. Also, BPA caused vascular congestion, hyperplasia (functional, reactive and atypical) of prostatic epithelium as well as tubular atrophy the rats while ML attenuated the observed lesions. Decreased localization of αSmooth muscle actin, vimentin and S100 proteins were observed in the BPA-treated rats while these decreases were ameliorated by ML. The present study has shown that sub-acute oral administration of BPA induced alterations in prostatic index, serum hormone levels, down-regulated protein localization and induced morphological lesions of the prostate gland in rats while concomitant treatment with intra-peritoneal ML ameliorated these conditions. Hence, low dose of ML can protect against BPA-induced toxicity of the prostate gland of rats.