This study investigated the relationship between enteroendocrine and mucus‐secreting cells distribution, the severity of colonic mucosal injury and intestinal motility in experimental colorectal carcinogenesis. Using a standardized murine model of colorectal carcinogenesis, eight‐weeks‐old female Wistar rats weighting 147.30 ± 29.15g were randomized into two groups receiving a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2‐dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci (ACF) were more frequent in DMH group compared to control group (P < 0.001). The number of enteroendocrine and mucus‐secreting cells, and intestinal motility was reduced in DMH animals (P < 0.05). The distribution of enteric neurons was similar in both groups. In DMH animals there was a direct correlation between colonic motility and distribution of enteroendocrine (R² = 0.68, P < 0.05) and mucus‐secreting cells (R² = 0.77, P < 0.05). Inverse correlation between the number of ACF, mucus‐secreting cells (R² = −0.57, P < 0.05), and enteroendocrine cells (R² = −0.74, P < 0.05) was also observed. There was inverse correlation between the severity of the mucosal lesion, the number of mucus‐secreting cells (R² = −0.83, P < 0.05) and enteroendocrine cells (R² = −0.96, P < 0.05). There was a direct correlation between nucleolar organizer regions (AgNOR) and ACF number (R² = 0.62; P < 0.01). Inverse correlation was also found between AgNOR, the number of mucus‐secreting cells (R² = −0.76; P < 0.001), and enteroendocrine cells (R² = −0.86; P < 0.001). Taken together, the results indicated that colonic malignant transformation is related to depletion of mucus‐secreting and enteroendocrine cells, which was a useful indicator of the evolutionary status of intestinal neoplasm, partially explaining the intestinal motility disorders in the early stages of colorectal carcinogenesis. Microsc. Res. Tech. 79:3–13, 2016. © 2015 Wiley Periodicals, Inc.