The greatest proportion of the hepatic clearance of haloperidol is by glucuronidation and by cytochrome P450 mediated oxidation. Releasing of transaminase enzymes from liver cells is known consequences of neuroleptic drugs, especially haloperidol. Free radicals may play an important role in the physiopathology of such disorders have hypothesized that during tardive dyskinesia, for instance, there are specific structural neuropathological changes and that cell membranes may be destabilized by the toxic action of free radicals produced during the chronic use of neuroleptics. This effect can be related, at least in part, to a reduction in specific endogenous antioxidant mechanisms, such as a decrease in reduced glutathione (GSH) levels. The aim of the study was to investigate the histopatholocigal changes and oxidative effects of haloperidol on hepatic tissue in chronic treatment with different doses. 30 adult male Wistar albino rats weighing 180~ 10 g were used. Rats were divided into 5 groups. Haloperidol was given 0.5, 1 and 2.5 and 5 mg/kg doses, once a day, intraperitoneally in 1 ml volumes, for 10 weeks. For control animals, 1 ml of distilled water was administered in the same protocol. The ethic guidelines for animals were obeyed. We observed dose dependent cellular degeneration, perilobuler infiltration of inflammation cells, congestion of central veins and epithelial proliferation of bilier tractus. Haloperidol induced a significant decrease in the superoxide dismutase (SOD) content at 1 and 2.5 mg/kg doses and decrease malonile dehydrogenase (MDA) content in 1 mg/kg doses (p < 0.05). These observations shows that higher doses ofhaloperidol cause a decrease in antioxidant content and this may cause of hepatotoxicity. Clinicians must avoid from using of high-dose haloperidol.