In stent restenosis (ISR) has been described as an unaccomplished tissue healing and its rate is particularly high in diabetic patients. Evidence has been collected which relates the formation of ISR proteoglycan-rich neointimal tissue to the accumulation and protracted activation of macrophages around the stent metal struts. Here, the in vitro activation of mononuclear cells adhering to stainless steel (a material of choice in stent manufacturing) from control and diabetic (types 1 and 2) subjects was assessed in the presence of different glucose levels. The results showed that cells from the control and type 1 diabetes groups produced significantly higher levels of TGF-beta1 when adhering on stainless steel (p = 0.04 and p = 0.01), but a significant PDGF-BB secretion was observed only in control subjects. When tested at physiological glucose concentration, the effect of the stainless steel on control cells was more pronounced. The present study shows that mononuclear cells adhering onto stainless steel secrete growth factors relevant to ISR. Cells from diabetic subjects seem to secrete relatively higher levels of PDGF under hyperglycaemic conditions regardless of the substrate exposed thus offering an explanation for the higher incidence of restenosis in these patients.