Abstract Background: Premature atherosclerosis has been recognized as a major co-morbid condition in systemic lupus erythematosus (SLE). Glucose-dependent insulinotropic polypeptide (GIP) is closely related to cardiovascular (CV) risk factors we aimed to evaluate GIP expression level in SLE and to explore the possible associations of GIP expression profile with (CIMT) insulin resistance (IR) and SLE disease activity. Methods: a cross-sectional controlled study comprising 170 SLE patients and 120 controls. GIP expression level was measured by multiplex polymerase chain reaction. The carotid intima-media thickness (CIMT) was measured. Serum GIP levels, homeostasis model assessments (HOMA-IR and HOMA-b), fibrinogen and homocysteine were measured. Results: In the SLE patients with IR, there were significantly higher values of serum GIP levels (37.99±13.64) compared SLE patients without IR (24.61±10.74) as well as the control group, (21.7±3.46) In addition, there were the significant positive correlation between GIP serum level and CV risks. Regarding GIP gene expression levels, there were significantly lower levels of GIP gene expression in SLE patients with IR (1.29±0.72) compared SLE patients without IR (2.43±0.61) as well as the control group. Receiver operating characteristic (ROC) analysis revealed that the diagnostic power of GIP expression was stronger than GIP serum levels in differentiating SLE from control. In conclusion, in the SLE group, there were lower GIP expression and higher serum levels than control, especially in IR subgroup. GIP expression and serum levels associated with CVD pathogenesis and progression. Keywords: systemic lupus erythematosus; GIP; Expression; CV; IR.