This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 mu g/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor alpha and interleukin 1 beta levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD.