Systemic lupus erythematosus is one of autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis with endothelial cell damage.The aim of the present work was to study the possible role of Angiopoietin - 2 as a recent inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker P-Selectin as well as various markers of the disease activity. The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group Π) and healthy normal control subjects (group Ш). All groups were subjected to measurement of plasma Angiopoietin-2 and P-Selectin by ELISA in addition to various laboratory investigations diagnosing SLE and all parameters of disease activity as: Hb, WBC´s, Platelets, ESR, serum creatinine, C3, C4 and 24 hour urine protein.The mean level of Plasma Ang-2 showed a high significant increase in active and inactive SLE patients than control subjects (p< 0.001) and in active than inactive SLE patients (p< 0.001). Mean level of Plasma P-Selectin showed a high significant increase in active SLE patients than inactive SLE patients and control subjects (p< 0.001). There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI, 24 h urine protein , ESR in all SLE patients as well as in active group. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4 in all SLE patients as well as in active group. In conclusion, plasma Ang-2 could be considered as a strong indicator of disease activity .Ang-2 does not primarily affect endothelial cell inflammation by itself but facilitates endothelial activation and subsequent leucocyte transmigration in the presence of various inflammatory stimuli as P-Selectin. There is possible involvement of Ang-2 in the pathogenesis of renal lupus.