Background: Overproduction of reactive oxygen species (ROS) causes increased lipid peroxidation, decreased intestinal epithelialbarrier integrity, and ultimately mucosal disruption and ulceration. Several studies have confirmed the antioxidant, antiinflammatory, and immunomodulatory properties of Spirulina Platensis (SP), edible blue-green algae, in various inflammatory diseases. In addition, natural honey, a source of phenolic and flavonoid compounds, is a powerful antioxidant, which can help preventchronic oxidative stress and subsequent inflammation. Objectives: In this study, we examined and compared the protective effects of SP and honey on ulcerative colitis induced by aceticacid (AA) in rats. Methods: Forty male rats were allocated into five groups (N = 8) and received pretreatment for 32 consecutive days. The administrationswere as follows: group 1 (control) and group 2 (AA-colitis group): normal saline, group 3: 1 ml honey/day, group 4: 1 mlhoney/day plus 1 g/kg SP, and group 5: 1 g/kg SP. Colitis was induced on the 30th day in groups 2 to 5. On day 32, the clinical activityscore was determined and anesthetized animals were sacrificed. Serum interleukin-6 (IL-6), IL-1 , tumor necrosis factor- (TNF- ), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), superoxide dismutase (SOD), myeloperoxidase (MPO), prostaglandin E2 (PGE2), malondialdehyde (MDA), nitric oxide (NO), and colonic weight/length ratio weredetermined. In addition, histopathological changes of the colon were observed microscopically. Results: Theinflammatory markers (PGE2, MDA, NO, IL-6, IL-1 , MPO, andTNF- ) were significantly lower in the pretreatment groupsthan in the AA-colitis group (P values < 0. 05). PGE2 [median (IQR)] of the honey, SP + honey, and SP groups was [0. 76 (0. 33)], [0. 75(0. 40)], and [0. 87 (0. 86)], respectively, compared to the AA-colitis group [2. 60 (2. 23)] (P values < 0. 041). MDA values were [6. 52 (3. 57)], [6. 09 (3. 59)], and [5. 85 (4. 92)] vs. [16. 60 (12. 03)] (P values < 0. 046) and IL-1 values were [42. 20 (8. 2)], [41. 76 (18. 10)], and [42. 93 (14. 09)]vs. [79. 54 (40. 79)] (P values < 0. 044). Also, SOD, GSH, GPx, and TAC [median (IQR)] were significantly higher in the pretreatmentgroups than in the AA-colitis group (P values < 0. 05). For example, TAC values of the honey, SP + honey, and SP groups were [0. 164(0. 08)], [0. 14 (0. 05)], and [0. 16 (0. 10)], respectively, vs. the AA-colitis group [0. 08 (0. 01)] (P values < 0. 028). Conclusions: Honey and SP are favorable foods in preventing oxidative stress and inflammatory diseases such as ulcerative colitis.