Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by sclerotic changes which affect the skin and internal organs. Interleukin-33 (IL-33) is a newly reported cytokine of the IL-1 family. Objective: The aim of this work was to determine serum levels of IL-33 in SSc patients and evaluate its association with clinical manifestations and disease subset. Methodology: The study included two groups. Group A included 40 adult patients diagnosed asSSc, these were subdivided into diffuse systemic sclerosis (dSSc) and limited systemic sclerosis (lSSc) groups. All patients were diagnosed according to the ACR criteria for SSc. Group B included 20 healthy adult persons (age and sex matched) as the control group. All patients were selected from the Rheumatology department Benha University Hospital. Serum IL-33 levels were examined by means of enzyme-linked immunosorbent assay. Result: mean serum level of IL-33 were highly significant in SS patients in comparison to control groups [p