Islet amyloid polypeptide (IAPP) is a beta cell hormone, which forms islet amyloid in non-insulin-dependent diabetes mellitus and may oppose insulin action and release. Therefore, the previously observed relative overexpression of IAPP compared with insulin in streptozotocin-treated rats could be unfavourable if it occurs in diabetes. Using quantitative in situ hybridization, we examined whether insulin treatment affected IAPP and insulin gene expression and their ratio at day 8 and 20 after induction of streptozotocin diabetes (plasma glucose approximately 30 mM). Total islet IAPP mRNA levels were less reduced than those of insulin at both time points. Differential regulation of the two hormones was further reflected by mean IAPP mRNA levels in the remaining islet cells being unaffected by streptozotocin treatment, whereas those of insulin were reduced. At both time points, insulin treatment decreased total islet levels of IAPP and insulin mRNA even more, IAPP mRNA levels being less reduced. Mean insulin mRNA levels, but not IAPP mRNA levels, in the remaining islet cells were reduced by insulin treatment. Between time points, total islet mRNA levels were higher at day 20, while mean mRNA levels in the remaining islet cells were unchanged, suggesting that regeneration of beta cells had occurred. In contrast, insulin gene expression was the same at both time points in insulin-treated rats, suggesting that insulin impaired insulin expression. To summarize, we found that IAPP and insulin were differentially expressed in experimental diabetes and that insulin treatment inhibited insulin, but not IAPP, gene expression. It is therefore unlikely that insulin will protect against amyloid formation and metabolic perturbations which may arise as a consequence of IAPP overexpression.