Frying in vegetable oil is a popular cooking and food processing method worldwide; as a result, the oils used for frying are widely consumed by the general public and it is of practical importance to better understand their health impacts. To date, the effects of frying oil consumption on human health are inconclusive, making it difficult to establish dietary recommendations or guidelines. Here we show that dietary administration of frying oil, which was prepared under the conditions of good commercial practice, exaggerated dextran sodium sulfate (DSS)-induced colitis in mice. In addition, to explore the potential compounds involved in the actions of the frying oil, we isolated polar compounds from the frying oil and found that administration of the polar compounds also exacerbated DSS-induced colitis in mice. Together, our results showed that dietary administration of frying oil exaggerated development of inflammatory bowel disease (IBD) in mice, and this effect could be mediated by the polar compounds in the frying oil.