Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP‐choline against the deleterious effects induced by Hg2+ on renal function was studied. CDP‐choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP‐choline guards mitochondria against Hg2+‐toxicity by preserving their ability to retain matrix content, such as accumulated Ca2+. This nucleotide also protected mitochondria from Hg2+‐induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP‐choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL‐1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg2+ and CDP, CDP‐choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine.