The immunomodulatory effects of Monascus-fermented Saccharina japonica extract on anti- and pro-inflammatory cytokines gene expression of THP-1 cells were evaluated. Extracts of fermented samples showed higher phenolic, flavonoid, protein, and reducing sugar contents than unfermented one. Fermented samples were rich in many bioactive compounds determined by GC-MS analyses and showed cell viability greater than 85% in MTS assay. Regarding the anti-inflammatory and pro-inflammatory activities of the different samples, Q-PCR analyses revealed that IL-10 gene expression in THP-1 cells was significantly higher (p<0.05) in cells treated with the SjMp or SjMk sample than those treated with the unfermented sample. Cells treated with the SjMp extract or lipopolysaccharide (LPS) showed significantly (p<0.05) higher relative gene expression of IL-4 cytokine than cells treated with SjMk or SjU extracts. The relative gene expression of IFN- was higher in cells treated with SjMp followed by LPS, SjMk, and SjU. TGF- expression was higher in LPS-stimulated cells followed by SjMk and other samples. Cells treated with SjMp exhibited significantly higher pro-inflammatory (IL-6, IL-8, TNF-, and NF-B) cytokine gene expression than cells treated with SjU. These results revealed that extracts from S. japonica fermented with Monascus spp. regulate cytokine gene expression.