Ulcerative colitis (UC) is a chronic intestinal inflammation. Common clinical symptoms are weight loss, diarrhea, ulcers, and inflammation. Aloe vera (AV) has several medicinal properties including antioxidant, anti-inflammatory analgesic, and improvement of gastric and skin ulcers. This study aimed to investigate the protective and therapeutic effects of AV gel on acetic acid-induced UC in rats. UC was induced in 48 rats by injection of 4% acetic acid into the rectum. Protective and treatment groups received treatments 7 days before and after the induction of colitis, respectively. The negative control group, the positive control group, and AV groups received distilled water, sulfasalazine, and 50 and 300 mg/kg of gel extract, respectively. Water and food intake and body weight changes were recorded. The extent of the mucosal ulcers, colon tissue thickening, and mucosal bleeding were scored by the Gerald classification system score (microscopy observations). Slides of tissues were prepared for pathologic assay using the modified Wallace method (macroscopic observations). The results of the macroscopic and microscopic examination showed protective and therapeutic effects of 50 mg/kg dose of AV on acetic acid-induced colitis in rats which reduces the inflammation, ulcers and tissue damage compared with negative control (p < 0.05). There were no significant changes in the amount of water and food intake, body weight changes, and colon weight in protective and treatment groups. Based on the results, AV gel could be used to improve the symptoms of UC, as well as prevent people who are susceptible to the UC.