The current study was conducted to investigate whether saffron has prophylactic effects on an experimental colitis mice model by evaluating the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in colon tissue, the colonic 5-HT level, assessing the cecal microbiota composition, and analyzing the changes in short-chain fatty acids in feces. This evidence concerns the gene IL6 and colitis.