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This study aimed to assess the anti-inflammatory effect of Lactobacillus casei 3260 (LC) alone and LC-fermented Gleditsia sinensis thorn (GST) extract in mouse model of type II collagen induced rheumatoid arthritis (RA). In our previous work, we confirmed the antiinflammatory effects of LC and GST against LPS-induced inflammation in vitro. In this study, LC and GST were fermented and their effects were assessed in an animal model of RA. Both LC and fermented GST (fGST) treatment reduced mice serum nitrite and total cholesterol and triggered myeloperoxidase (MPO) activity. In addition, both LC and fGST reduced inflammation-related serum biomarkers such as tumor necrosis factor-α, interleukin (IL)-6, IL-17, and IL-1β. As per the morphological analysis, both LC and fGST protected hind paw joints against RA, and its related mRNA markers improved. Finally, arthritis scores were measured as an indicator of RA of the whole experimental period; the scores suggested that both LC and fGST protect against collagen-induced RA-related inflammation in a mouse model.