This study investigates the effect in the rat of chronic (CdCl₂ intoxication 500µg Cd²⁺/kg, daily IP injection during 5 days) on the renal function and the changes in tight junction proteins, Claudin-2, Claudin-3 and Claudin-5, present in rat kidney. We also studied the effect of co-administration of ZnCl₂ (500µg Zn²⁺/kg) during chronic CdCl₂ intoxication. Our results indicate that: 1) most of the filtered cadmium is reabsorbed within the kidney; 2) chronic Cd²⁺ intoxication can induce a change in renal handling of ions without altering glomerular filtration rate; 3) a delayed nephropathy, showing Fanconi- like features, appears more than 5 days after the end of CdCl₂ exposure; 4) epithelial integrity is altered by chronic Cd²⁺ intoxication affecting the expression and localization of the claudins tight-junction proteins; 5) co-treatment with Zn²⁺ protects against the renal toxic effects of Cd²⁺ preventing altered claudin expression and by inhibition of apoptosis. In conclusion, these results show that Cd²⁺ toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins. Finally, zinc supplementation may provide a basis for future treatments.