Background: miRNA-155 (miR-155) became a focus in several studies because of its essential functions in autoimmune diseases and inflammatory responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Objective: We aimed in the current study to explore the expression profile of micro RNA-155 in SLE and evaluate its association with the clinical, immunological, and electrophysiological tests of patients with peripheral neuropathy (PN). Patients and methods: Ninety-five recently diagnosed systemic lupus erythematosus (SLE) patients according to 2012 Systemic Lupus International Collaborating Clinics classification criteria were enrolled in addition to 100 controls. Peripheral nerve conduction was evaluated by performing nerve conduction studies (NCSs). The serum miRNA-155 expression profiles were measured using a quantitative real time-polymerase chain reaction (qRT-PCR). Results: Of the 95 SLE patients, PN was present in 35 patients (36.8%). The serum miR-155 expression levels were upregulated the in serum of SLE patients (1.17±0.21) compared to controls (0.826±0.169), P < 0.001. Among SLE groups, patients with PN had a higher level of miR-155 expression (1.24±0.1781) than patients without PN (0.913±0.046), P < 0.001. There was a significantly positive correlation of miR-155 expression levels with The Toronto Clinical Scoring System (TCSS), immunological markers, and electrophysiological tests of median and ulnar nerve. Conclusion: This is the first Egyptian study report that miR-155 expression profile is upregulated in SLE patients especially patients with PN indicating miRNA-155 might be a potential biomarker for the diagnosis and treatment of SLE related PN.