It is generally accepted that proinflammatory cytokines secreted by macrophages/monocytes as well as cytotoxic T cells are responsible for pancreatic B-cell destruction in animal models of autoimmune diabetes and presumably in insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to evaluate the production of interleukin (IL)-13-a Th2 cells derived anti-inflammatory cytokine, by peripheral blood of newly diagnosed IDDM patients and their first degree relatives with a low or high risk of IDDM development. The study was carried out in 20 patients with a recent onset of type 1 diabetes, their first degree relatives with high (with DRB1*03 and/or DRB1*04 HLA class II alleles and two or more autoantibodies directed against pancreatic B-cell antigens) (n = 20) or a low (with DQB1*0602 allele) risk of type 1 diabetes development (n = 10) and a control age matched group of healthy volunteers (n = 18). IL-13 concentrations in supernatant of 72 h cultures of peripheral blood after incubation with phytohemagglutinin (PHA) or PHA+ insulin were quantified by enzyme-linked immunosorbent assay (ELISA). The levels of IL-13 in the supernatants were significantly lower in at high risk of IDDM first degree relatives of diabetic patients (P < 0.02), higher in subjects with low genetic risk of diabetes type 1 (P < 0.02), and normal in IDDM patients in comparison to the control group. We have also observed that the adding of human insulin to the cultures resulted in a significant increase of in vitro IL-13 production in prediabetics, but not in the other studied groups. In conclusion our findings suggest that the IL-13 alterations could play an important role in the pathogenesis of type 1 diabetes. We would speculate that IL-13 as an anti-inflammatory cytokine and a mediator of the Th2 pathway could be the potential therapeutic approach in the prevention of type 1 diabetes.