A number of studies have shown that palladium nanoparticles are able to exert some adverse health effects, such as concentration-dependent cytotoxicity, induction of apoptosis and alterations of the release and expression of numerous cytokines. Nevertheless, our current knowledge of the potential toxic effects induced by exposure to these nanoparticles is far from being complete. For this reason, the present study assessed the possible renal toxicity of palladium nanoparticles by investigating urinary excretion of retinol binding protein, β2-microglobulin and albumin in female Wistar rats intravenously exposed to different nanoparticle concentrations (0.012, 0.12, 1.2 and 12 µg/kg) and by carrying out a morphological observation of the kidneys of treated animals. Results showed a significant increase in urinary retinol binding protein and β2-microglobulin levels in rats that were administered 12 µg/kg compared to controls. Moreover, an ultrastructural study of the kidneys revealed significant alterations in the proximal and distal tubular epithelium were observed, with a range of severity, in all experimental conditions. Collectively, our findings suggest that exposure to palladium nanoparticles is able to induce a significant renal tubular dysfunction, whereas it does not seem to affect kidney glomerular filtration. However, further studies are needed to confirm our results, to understand the molecular mechanisms of toxic action and to evaluate the potential adverse effects of these nanoparticles also on the glomerular section of the kidney.