This study explored and investigated how zearalenone (ZEA) affects the morphology of small intestine and the distribution and expression of ghrelin and proliferating cell nuclear antigen (PCNA) in the small intestine of weaned gilts. A total of 20 weaned gilts (42-day-old, D × L × Y, weighing 12.84 ± 0.26 kg) were divided into the control and ZEA groups (ZEA at 1.04 mg/kg in diet) in a 35-d study. Histological observations of the small intestines revealed that villus injuries of the duodenum, jejunum and ileum, such as atrophy, retardation and branching dysfunction, were observed in the ZEA treatment. The villi branch of the ileum in the ZEA group was obviously decreased compared to that of the ileum, jejunum and duodenum, and the number of lymphoid nodules of the ileum was increased. Additionally, the effect of ZEA (1.04 mg/kg) was decreased by the immunoreactivity and distribution of ghrelin and PCNA in the duodenal and jejunal mucosal epithelial cells. Interestingly, ZEA increased the immunoreactivity of ghrelin in the ileal mucosal epithelial cells and decreased the immunoreactivity expression of PCNA in the gland epithelium of the small intestine. In conclusion, ZEA (1.04 mg/kg) had adverse effects on the development and the absorptive capacity of the villi of the intestines; yet, the small intestine could resist or ameliorate the adverse effects of ZEA by changing the autocrine of ghrelin in intestinal epithelial cells.