The role of several cytokines has been suggested in the pathogenesis and progression of systemic lupus erythematosus disease (SLE). In addition, CD4+T cell abnormalities have been conceivable to be primarily significant for the immune dysfunction of systemic lupus erythematosus (SLE). Interleukin-16 (IL-16) is a CD8+ T cell-derived cytokine that induces activation of CD4+ T-cells recruited to sites of inflammation associated with several diseases, such as rheumatoid arthritis, bronchial asthma and SLE.The objective: The objective of this work is to investigate the serum level of IL-16 in SLE patients and to correlate it with the clinical finding, disease activity using (SLAM) index, laboratory parameters and medical therapy.The methods: Forty female patients diagnosed as SLE and twenty healthy adults females as control group were subjected to measurement of serum level of IL-16 using ultrasensitive enzyme linked immunosorbant assay [ELISA].The Results: A significant increase in the IL-16 serum level in SLE patients compared with the control group. IL-16 level increases with the disease activity measured by SLAM index. IL-16 was highly significant correlation with 24-hour urine protein, serum creatinine level. High IL-16 serum level showed no statistically significant association with various clinical features except (hypertension & Raynaud’s phenomenon), other laboratory finding except for (leucopenia & casts in urine) and different lines of treatment of SLE patients.In conclusion: Serum IL-16 levels can be considered as useful indicator of disease activity in SLE patients as well as lupus nephritis.