【Objective】To observe the effects of folic acid (FA) supplementation on the expression of Flotillin-1 and β-amyloid protein (Aβ) metabolism-related proteins in the brains of inflammation-stimulated AD mice.【Methods】Twenty-seven 6-month-old male APP/PS1 mice were randomly divided into AD, AD+LPS, and AD+LPS+FA groups, with 9 mice in each group. 9 same-month-old C57BL/6J male mice were used as the wild control group (Control). The AD+LPS+FA group was given folic acid supplemented feed (8 mg/kg) for three months of intervention, while the other three groups were fed normal feed. Lipopolysaccharide solution (LPS, 250 μg/kg/day) was injected intraperitoneally into mice in the AD+LPS group and AD+LPS+FA group one week before the end of the experiment, and saline was injected into the remaining two groups. The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1-40 and Aβ1-42 levels of mice in each group were detected by ELISA, Flotillin-1 protein expression in brain tissue was detected by Western blot, and immunofluorescence double-labeling was used to detect the co-expression of Flotillin-1 in the cortical region of the brain and Aβ1-42/APP/PS1/ BACE1 co-expression. 【Results】 After ANOVA analysis, compared with the Control group, mice in the AD group had elevated serum TNF-α and IL-6 levels (P < 0.05), elevated levels of Aβ1-40 and Aβ1-42 (P < 0.05), increased expression of Flotillin-1 protein (P < 0.05), and increased co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical region of brain tissue (P < 0.05); Compared with the AD group, mice in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain (P < 0.05), and increased expression of double-labeled positive proteins in the cortical region of brain tissue for Flotillin-1 and Aβ1-42/APP/BACE1 (P < 0.05) ; Compared with the AD+LPS group, mice in the AD+LPS+FA group had lower in vivo inflammation levels and Aβ content in the brain (P < 0.05), lower brain tissue Flotillin-1 protein expression (P < 0.05), and lower co-expression of Flotillin-1 with Aβ1-42/APP/PS1/BACE1 proteins in the cortical region of brain tissue (P < 0.05). 【Conclusion】 Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.