2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide of the chlorophenoxy class and the second most widely used herbicide applied to several different crops worldwide. Environmental factors, especially those related to diet, strongly affect the risk of developing cancer of the gastrointestinal tract. There is currently no evidence to determine whether there is an association between 2,4-D exposure and gastrointestinal disorders. We evaluated the histological effect of chronic oral and inhalation exposure to 2,4-D on the digestive tract of rats. Eighty male adult albino Wistar rats were divided into 8 groups (n=10): two control groups, one for inhalation and one for oral exposure, and 6 groups exposed orally or by inhalation at three different concentrations of 2,4-D [3.71×10-3 grams of active ingredient per hectare (gai/ha), 6.19×10-3 gai/ha, and 9.28×10-3 gai/ha]. The animals were exposed for 6 months. The esophagus, stomach, and intestine were collected for histopathological analysis. Animals exposed to 2,4-D had hyperkeratosis of the esophagus, regardless of the exposure route. All animals exposed to a higher concentration of 2,4-D orally presented mild dysplasia of the large intestine. In the small intestine, most animals exposed to moderate and high concentrations of 2,4-D had mild dysplasia. No gastric changes were observed in any of the groups studied. Chronic exposure to 2,4-D, especially at moderate and high concentrations, regardless of the exposure route, caused reactive damage to the esophagus (hyperkeratosis) and dysplastic changes to the intestine.