Background: Dormex, which is used as agricultural fertilizer, contains cyanamide as an active ingredient. Pomegranate fruits enclose numerous polyphenols that guard normal cells against oxidative stress. Aim of the work: to study the hepatotoxic effects of Dormex and assess the protective capacity of pomegranate seed extract (PSE) in rats after 3 months of oral administration. Material & methods: Sixty mature male albino rats were distributed to; Group I, II: rats were given 0.1 ml distilled water/kg/day and 400 mg/kg/day of pomegranate seed extract (PSE), respectively. Group III: divided into two subgroups in which rats received 30 & 60 mg/kg/day Dormex, respectively. Group IV: divided into two subgroups in which rats were given the same dose of Dormex plus PSE. Body and liver weights, serum albumin, total bilirubin and liver enzymes were assessed. Hepatic malondialdehyde (MDA), glutathione reductase and catalase activities were evaluated. Liver specimens were studied with H. &E., Mallory's trichrome and caspase-3 immunostaining. Results: The hepatic index, liver enzymes, bilirubin, and MDA were significantly increased (P˂0.001), while albumin, glutathione reductase, and catalase were lowered significantly in rats of experimental groups compared to the control (P˂0.001). All these assessed parameters were within normal range in the protected groups. The histopathological changes included liver inflammation, degeneration and fibrosis, in addition to apoptosis. Treatment with PSE markedly prevented the occurrence of these abnormalities. Conclusion: Cyanamide prompts oxidative stress that compromises the liver function and eventually liver fibrosis results. These toxic effects are dose related. The PSE exhibits hepatoprotective effects and highlights the possibility of its use as a protective agent in individuals at high risk of Dormex toxicity.