Abstract: This study investigated the effect of high-grain (HG) diets on microbial fermentation, epithelial tissue morphology, alkaline phosphatase activity and the quantity of microbial flora in the small intestine of goats. Twelve goats were randomly allocated to two groups (6 in each group) and were fed a hay (0% grain) or HG diet (75% grain) for 6 weeks. After 6 weeks of feeding, the goats were slaughtered to collect small intestinal digesta and tissue for analysis. The results showed that: 1) Compared with the hay group, HG feeding significantly increased the concentrations of total volatile fatty acid (P=0.015), propionate (P=0.008), butyrate (P=0.004) and isobutyrate (P=0.035), while it significantly decreased the concentration of lactic acid (P=0.008). However, HG diet feeding did not influence pH or the concentrations of acetate, valerate, isovalerate and LPS in jejuna digesta (P>0.05); Compared with the hay group, HG diet increased the concentrations of total volatile fatty acid (P=0.007), propionate (P=0.013), butyrate (P=0.008), valerate (P<0.001), lactic acid (P=0.008) and lipopolysaccharide levels (P<0.001), while it decreased the pH value (P=0.005) in ileal digesta. There were no significant differences in the concentrations of acetate, isobutyrate, isovalerate between the hay and HG groups (P>0.05).2) Compared with the control, HG feeding significantly increased villi height and crypt depth in the duodenum, jejunum and ileum tissue (P<0.001). The ratio of villus height to crypt depth (V/C) increased in the jejunum (P=0.024). Transmission electron micrographs of jejunum and ileum tissue during the HG diet displayed a deterioration of the tight junction.3) Compared with the control, HG diets significantly increased the alkaline phosphatase activity of ileal mucosa (P<0.05), but had no influence on the alkaline phosphatase activity of jejunum mucosa (P>0.05). 4) Real-time PCR analysis showed that in ileum digesta the 16S rRNA gene copies of Bacteroidetes from the HG group were significantly lower than for the hay group (P=0.037). The HG group showed an increase in the ratio of Firmicutesto Bacteroidetes (P<0.001), while there was no significant difference in the 16S rRNA gene copies of Firmicutes (P>0.05). No significant differences (P>0.05) between the hay and HG groups’ jejunum digesta were observed in the 16S rRNA gene copies of Bacteroidetes and Firmicutes, or in the ratio of Firmicutes to Bacteroidetes. In summary, these results indicate that feeding goats high proportions of grain can significantly influence the morphological characteristics of ileal epithelium and microbial fermentation in ileal digesta, and may have a negative effect on the health of goats.