In the present study, we tested the hypothesis whether agmatine and spermidine, metabolites of arginine metabolism, share the pharmacological activities of argi- nine reducing collagen accumulation in the diabetic kidney. Eleven db/db mice were administered agmatine and 12 db/db mice spermidine (50 mg/kg body weight). Ten db/db mice received no treatment as negative controls and 10 db/db mice were treated with aminoguanidine (50 mg/kg body weight) as positive controls. Mean kidney OH-proline content reflecting kidney collagen content and mean CML concentration were significantly higher but acid solubility of collagen significantly lower in the untreated group than in the treated groups. Agmatine, although missing the α-amino group and the carboxyl group, and spermidine, although missing the guanidino group, thus still revealed the arginine activity. We hypothesize that the strongly nucleophilic structure of polyamines common to all active compounds is able to block reactive carbonyls.