Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases.