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We tested the hypothesis if thymoquinone (2‐isopropyl‐5‐methyl‐1,4‐benzoquinone) could ameliorate renal oxidative damage and proliferative response induced by mercuric chloride (HgCl₂) in rats. HgCl₂ (3 mg/kg) was administered subcutaneously to each one of two groups of rats: (i) HgCl₂–thymoquinone group that received thymoquinone (10 mg/kg/day); and (ii) HgCl₂ group that received vehicle instead of thymoquinone. A third group of rats was reserved as control group. Rats were killed 24, 48 and 72 hr after HgCl₂ administration for histological and biochemical studies. Our findings show that treatment with thymoquinone offers imperative protection from HgCl₂‐induced nephrotoxicity. The deterioration of antioxidant enzymes, increment of serum creatinine and histological damage caused by HgCl₂ are markedly improved by thymoquinone treatment. Apoptosis and proliferative reactions are also reduced …