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The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA)(identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters. Moreover, serum levels of TNF-α and IL-6 were analysed before and after M2000 therapy compared to healthy controls using enzyme linked immunosorbent assay method. We found a significant increase in the count of red blood cells and also hemoglobin (Hb) concentration (0.9 g/dL) in anemic patients after 12 weeks of M2000 therapy (p< 0.02 and p< 0.01, respectively). Furthermore, our results showed an improvement in Hb level (0.45 g/dL) even in non-anemic patients who were treated by M2000 (p< 0.04). The leukocytosis in RA patients, significantly decreased in both anemic and non-anemic patients after 12 weeks of M2000 therapy (p< 0.02 and p< 0.03, respectively). The percent of neutrophils significantly increased in anemic patients (p< 0.01) while in non-anemic patients it significantly decreased after 12 weeks of M2000 therapy (p< 0.01). The serum levels of IL-6 and TNF-α significantly decreased after 12 weeks of M2000 therapy (p< 0.01 and p< 0.04, respectively). M2000 improves hematological parameters in RA patients by its …