Using diffusion kurtosis imaging (DKI) to evaluate the brain changes, the therapeutic effect and mechanism of tetramethylpyrazine in rats with dementia induced by lipopolysaccharide. Thirty-six male Sprague-Dawley rats were randomly divided into control group and five groups pretreated with sham operation, lipopolysaccharide(150ug) and three doses of tetramethylpyrazine(5, 10, and 20 mg/mL respectively). The Morris water maze test was used to evaluate cognitive ability. DKI and histology were performed. Low-dose of tetramethylpyrazine pretreated rats showed lower escape latency(6th day: 15.92seconds(s) vs. 5.11 s, P = 0.001), spent more time in the target quadrant(15.67 s vs. 29.83 s, P = 0.009) and crossed the platform area more frequently(3.50 vs. 9.17, P = 0.001) than rats in the LPS-treated group. Compared to sham group, the fractional anisotropy (FA), axial diffusion (Da), mean kurtosis (MK), and axial kurtosis (Ka) values in the cortex of lipopolysaccharide group were lower (P = 0.021,0.003,0.003,0.001,respectively).The MK, Ka, Kr, and FA values in the hippocampus of the lipopolysaccharide group were higher (P = 0.01, 0.026,0.007,0.003,respectively),while MD and Da values were lower (P = 0.045,0.044, respectively). Tetramethylpyrazine-pretreated rats showed higher values of FA, MD, Da, MK, and Ka in the cortex, lower MK, Ka, Kr, and FA values and higher MD,Da values in the hippocampus than the lipopolysaccharide group. Histologically, prominent inflammatory cells infiltration in the brain parenchyma of lipopolysaccharide group were observed, while groups pretreated using tetramethylpyrazine were alleviated. Tetramethylpyrazine can improve cognitive dysfunction induced by lipopolysaccharide. DKI can sensitively detect microstructure integrity of brain parenchyma in a non-invasive manner.