The health effects of soy supplementation in (post)menopausal women are still a contro-versial issue. The aim of the present study was to establish the effect of the soy isoflavones(SIF) present in a commercially available supplement on ovariectomized rats and to inves-tigate whether these rats would provide an adequate model to predict effects of SIF in(post)menopausal women. Two dose levels (i.e. 2 and 20 mg/kg b.w.) were used to charac-terize plasma bioavailability, urinary and fecal concentrations of SIF and changes in geneexpression in peripheral blood mononuclear cells (PBMC). Animals were dosed at 0 and 48 hand sacrificed 4 h after the last dose. A clear dose dependent increase of SIF concentrationsin plasma, urine and feces was observed, together with a strong correlation in changes ingene expression between the two dose groups. All estrogen responsive genes and relatedbiological pathways (BPs) that were affected by the SIF treatment were regulated in bothdose groups in the same direction and indicate beneficial effects. However, in general nocorrelation was found between the changes in gene expression in rat PBMC with those inPBMC of (post)menopausal women exposed to a comparable dose of the same supplement.The outcome of this short-term study in rats indicates that the rat might not be a suitablemodel to predict effects of SIF in humans. Although the relative exposure period in this ratstudy is comparable with that of the human study, longer repetitive administration of ratsto SIF may be required to draw a final conclusion on the suitability of the rat a model topredict effects of SIF in humans.