Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of conditions that are thought to be mediated through the development of autoreactive immunoresponses. Inflammatory bowel disease (IBD) is common autoimmune disease that affects many individuals worldwide. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, the effect of Lycogen, a potent anti-inflammatory agent, was evaluated in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen reduced the expressions of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in female BABL/c mice. In addition, the increased number of bacterial flora in the colon induced by DSS was amelirated by Lycogen. The histological score of intestinal inflammation in 5% DSS-treated mice after oral administration of Lycogen was lower than that of control mice. Meanwhile, Lycogen dramatically prolonged the survival of mice with severe colitis. These findings identified that Lycogen is an anti-inflammatory agent with the capacity to ameliorate DSS-induced colitis.