Although an accumulating body of evidence indicates that levels of prostaglandin E ₂ (PGE ₂ ) in human and rodent colon cancers are higher than those in surrounding normal tissues, the precise contribution of PGE ₂ to the process of colon cancer development has still been unclear. Therefore, we designed a study using a well-established azoxymethane (AOM)-induced colon carcinogenesis in male F344 rat model to investigate whether administration of exogenous PGE ₂ has a real impact on colon carcinogenesis. Intraperitoneal PGE ₂ injections (7.7 µg) once a week for 25 weeks significantly increased the AOM-induced colon tumor incidence (percent rats with tumors, 92 versus 53%, P < 0.05), especially adenocarcinomas (92 versus 47%, P < 0.05), and multiplicity (number of tumors per rat, 2.8 versus 1.0, P < 0.05). PGE ₂ treatment significantly increased 5-bromo-2′-deoxyuridine (BrdUrd) labeling index (11.8 versus 9.7%, P < 0.05) and reduced apoptotic index (0.34 versus 0.53%, P < 0.05) in colon cancers induced by AOM. PGE ₂ exhibits its physiological functions through binding to E-prostanoid (EP) membrane receptors EP _1-4 . All four types of EP receptors were detected in AOM-induced colon cancers using reverse transcription–polymerase chain reaction (RT–PCR). Our results provide evidence that PGE ₂ enhances colon carcinogenesis through induction of cell proliferation and reduction of apoptosis.