The contribution of anti-inflammatory cytokines to rheumatoid arthritis (RA) is not fully comprehended. In the current research we assessed the serum concentration of interleukin (IL)-37 anti-inflammatory cytokine in RA, studied its association to disease activity score 28 (DAS28) and investigated single nucleotide polymorphism (rs2723176) of IL-37 gene as a threat for RA development. The case-control study included 60 RA patients and 30 normal control individuals. Serum IL-37 was assessed by ELISA and genotyped by “sequence-specific primer-polymerase chain reaction (SSP-PCR)”. The mean IL-37 was elevated in RA patients (69.42 ng /l ± 62.99) compared to control individuals (14.66 ng /l ± 23.58, p < 0.001). IL-37 tended to increase with age where highest levels were noted in patients more than 60 years (p = 0.037). No Gender influence was found on IL-37 level (p>0.05). At best cut-off value of 31.5 ng/ l, IL-37 had a sensitivity of 73.3% and specificity of 83.3%. No correlation of IL-37 with DAS 28 score was observed (r=0.1497, p=0.2535). For IL-37 (rs2723176) gene polymorphism, C/C genotype was prevailing in both RA (90%) and normal controls (93.3%) compared to A/C or A/A. Also, no variation was found between patents and controls in regard to C/C genotype (OR = 0.643, 95% CI (0.122-3.39, p=0.603). The mean IL-37 concentration in RA patients with C/C genotype (59.70± 67.92) was not different from AC genotype (80.54± 94.18, p=0.4748). We concluded that serum IL-37 had the implication as a diagnostic marker in RA. However, it did not correlate with clinical severity of the disease. Meanwhile, IL-37 (rs2723176) gene polymorphism did not seem to be as a risk factor for RA, nor contributed to the increase of IL-37 level among patients.