Systemic lupus erthematosus (SLE) is a prototype of autoimmune disease characterized by tissue deposition of autoantibody immune complex formation. However, etiology of disease remains unclarified. Defects of T lymphocytes lead to loss of immunological tolerance and support autoantibody production suggested that they may consistently have a central role in pathogenesis of SLE. Notch signaling is an evolutionarily conserved pathway responsible for thymocyte development, activation, proliferation, differentiation and T cell functions. Several evidences suggest Notch signaling involvement in autoimmune disorders. The aim of this study was to investigate the correlation of Notch1 receptor expression in T lymphocytes with disease progression. Twenty-two Thai SLE patients and eleven healthy controls were recruited for the study. Notch1 expression in PHA-stimulated T lymphocytes of SLE patients that indicated significantly defective regulation of Notch1 in activated T lymphocytes of SLE patients with active stage (p=0.025) while stimulated T lymphocytes of SLE patients with inactive stage were indifferent expression of Notch1 compared with healthy controls that quantified by real-time RT-PCR. It was confirmed by conventional RT-PCR that showed deceleration of Notch1 expression in SLE (p=0.015). As well as Notch1 protein expression, it was downregulated in active SLE compared to controls and inactive SLE (p=0.001 and 0.037, respectively). However, Hes1 that was target of Notch signaling did not reduce expression in SLE T lymphocytes. Moreover, proliferation capacity in SLE patients did not defect. These results showed converse correlation of Notch1 expression with severity of SLE. The data reveal the defective Notch1 in T cells that is possibly uncovered new factor of pathogenesis in SLE.