This study aimed to determine the effect of excessive fluoride (F) on the morphological characteristics of the small intestine and the contents of serum cytokines in rats. A total of 48 3-week-old healthy female Sprague-Dawley rats were randomly divided into four groups (n?=?12). The control group was given deionized distilled water, while the F treatment groups were treated with water containing 25, 50, and 100 mg F–/L. After 70 days of treatment, the duodenum, the jejunum, and the ileum were collected to measure the developmental parameters and the distribution of intestinal glycoproteins, goblet cells, and mast cells through Pannoramic Viewer, Periodic Acid-Schiff (PAS) staining, Alcian blue and periodic acid-Schiff (AB-PAS) staining, and toluidine blue staining, respectively. The contents of cytokines, namely, interleukin (IL)-1?, IL-2, IL-6, and tumor necrosis factor (TNF)-?, in serum were detected via enzyme-linked immunosorbent assay (ELISA). Results showed that the villus height, crypt depth, villus height to crypt depth ratio, goblet cells, glycoproteins, and mast cells of the small intestine significantly decreased (P?<?0.05 or P?<?0.01) in the F treatment group. The contents of IL-1?, IL-2, IL-6, and TNF-? were significantly lower in the F treatment group than in the control group (P?<?0.05 or P?<?0.01). In summary, excessive F intake impaired intestinal development and immune function by decreasing the developmental parameters and the distribution of immune cells, glycoproteins, and cytokines.