Aims: Podocytes are terminally differentiated cells of the glomerulus which play a crucial role as a final barrier to protein loss. Injury of podocytes disturbs this barrier function and ends up in glomerulosclerosis. The peptide adrenomedullin (AM) and its receptors are compounds which may exert protective effects when podocytes are exposed to oxidative stress. The aim of our work was to characterize the expression of AM and its receptors in differentiated mouse and human podocytes in culture and to examine their answer to oxidative stress. Furthermore, we investigated the cAMP answer of differentiated podocytes to treatment with adrenomedullin as possible protective pathway. Methods: Immortalized differentiated podocytes in culture were examined by RT-PCR, western blotting and immuncytochemistry for AM, AM2 and the receptor proteins CRLR, RAMP 2, RAMP 3 and ADMR. Mouse podocytes were treated by 250 mM H₂O₂ for 30 minutes, after which expression of AM and CRLR was measured by RT-PCR. After treatment of human podocytes with 50 nM, 100 nM and 200 nM adrenomedullin for 1, 3 and 5 minutes, intracellular cAMP production was measured by ELISA. Results: Both differentiated mouse and human podocytes in culture possess an adrenomedullin system including the peptides AM and AM2 and the receptor proteins CRLR, ADMR and RAMP 2. The receptor protein RAMP 3 was only found in mouse and not in human podocytes. After treatment of differentiated mouse podocytes with H₂O₂ a time-dependent rise in the expression of AM and its receptor CRLR could be shown. Furthermore, adrenomedullin increased the production of intracellular cAMP in differentiated human podocytes. Conclusion: Upregulation of adrenomedullin and its receptors may play a protective role upon oxidative stress in differentiated podocytes.