We assessed the implication of PPAR deficiency in pregnancy out-come and neonatal survival, and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR-null mice (OR=14.33; P = 0.013). Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR-null mice (OR=4.28; P = 0.011). In the pups born to diabetic dams, the offspring mortality, due to the absence of PPAR was enhanced, i.e. 27.7% in WT mice vs. 78.9% in PPAR-null animals (OR=11.48; P < 0.001). Moreover, we observed that Th1/Th2 balance was shifted to a pregnancy protecting Th2 phenotype in WT diabetic dams and to a noxious Th1 phenotype in PPAR-null mice with diabetic pregnancy (DP). Furthermore, offspring born to diabetic WT dams were hyperinsulinemic and hyperglycaemic, and they exhibited up-regulated profile of Th2 cytokines while those born to diabetic PPAR-null dams were hypoinsulinemic and hyperglycaemic, and they showed down-regulated profile of Th2 cytokines. However, IFN-, a Th1 cytokine, was up-regulated in the offspring of both diabetic WT and PPAR-null dams. Altogether, our results suggest that PPAR deficiency in mice may be implicated in the increase in maternal abortion, neonatal mortality and T cell differentiation.