OBJECTIVE: To study the effects of Xixin decoction (XXD) on O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of tau proteins in rat brain with sporadic Alzheimer disease (SAD), and discuss its possible mechanism on prevention and treatment of SAD. METHODS: The rat model of SAD was established by intracerebroventricular injection of streptozotocin. The specific pathogen free male Sprague-Dawley rats were randomly divided into sham-operation group (S), model group (M), donepezil group (D), XXD at a low dose group (XL), XXD at a medium dose group (XM) and XXD at a high dose group (XH). After treatment and praxiology test, immuno-histochemistry and western blotting were used to detect O-GlcNAc glycosylation level of tau proteins in rat brain with SAD. O-GlcNAc glycosylation and expression of tau proteins were detected by O-GlcNAc-specific antibodies RL2 and CTD110.6. RESULTS: O-GlcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significantly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups (P0.05). CONCLUSION: XXD can significantly improve O-GlcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hyperphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological process of SAD.