Effects of rectally injected prostaglandin E2 (PGE2) in rats with dextran sodium sulphate (DSS)‐induced colitis were investigated in terms of histopathology, local myeloperoxidase (MPO) activity, local mRNA expression of interleukin‐1β (IL‐1β), tumour necrosis factor‐α (TNF‐α) and growth‐regulated gene produced/cytokine‐induced neutrophil chemoattractant (GRO/CINC)‐1, and secretion of TNF‐α and GRO/CINC‐1. In animals with no PGE2 treatment, DSS‐induced erosion and ulceration were particularly severe in the rectum and extended to the proximal colon. Neutrophil infiltration was characteristically present in the lesions and surrounding mucosa. MPO activity at lesion sites was increased. IL‐1β and GRO/CINC‐1 mRNA expression was increased, while TNF‐α mRNA expression was significantly decreased. GRO/CINC‐1 secretion was increased but a similar elevation of TNF‐α was not detected. In the PGE2‐treated group, lesion formation was inhibited grossly and microscopically. Neutrophil infiltration and MPO activity in and around lesions were lessened. The reduction in TNF‐α mRNA expression and secretion was not affected by PGE2. The expression of mRNA for IL‐1β and GRO/CINC‐1 was reduced, as was the secretion of GRO/CINC‐1. As mRNA expression and secretion of cytokines in lesions of non‐PGE2‐treated animals was similar to that reported in human ulcerative colitis, rectal injection of PGE2 may prove to be an effective therapy.