Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of cell surface receptors that have activating or inhibiting functions in leukocytes through their intracytoplasmic immunoreceptor tyrosine-based activating motifs (ITAMs) and inhibitory motifs (ITIMs). LILRA3 lacks transmembrane and cytoplasmic domains, suggesting that it may be secreted. Although LILRA3 function is unknown, its high structural homology to activating LILRA1 and A2 indicate that it may act as antagonist or agonist to these receptors. Clinically, LILRA3 may have a role in a number of immune-related diseases. A recent finding showed that individuals who lack the LILRA3 gene have a higher incidence of multiple sclerosis, suggesting that LILRA3 may regulate inflammatory responses. However to date, expression studies of LILRA3 have been limited to mRNA. Here we developed an ELISA to detect LILRA3 protein in serum. To investigate whether LILRA3 plays a role in chronic inflammation, we examined its expression in serum and synovial fluid of patients with rheumatoid arthritis (RA).For the first time, we demonstrate LILRA3 protein expression in serum with increased levels in serum and synovial fluid of patients with RA compared to osteoarthritis or normal subjects. The level of LILRA3 in RA correlated with disease activity score. These findings indicate that LILRA3 may play a role in the pathogenesis of RA.