Central nervous system inflammation is associated with neurodegenerative diseases and is thought to play a part in the pathophysiological cascade leading to cognitive impairment. Madecassoside (MA) has shown potential for the treatment of neuroinflammation. Lipopolysaccharide (LPS) can be used to establish an animal model of cognitive dysfunction induced by neuroinflammation. Intravoxel incoherent motion (IVIM) may potentially provide diffusion and perfusion data. To investigate the effect of MA on neurocognitive impairment induced by LPS in rats, and to explore the changes of brain microstructure and microcirculatory perfusion by IVIM imaging. Prospective. Thirty-six male Sprague-Dawley rats were randomly divided into six groups (control group, sham operation group, LPS group, low-dose MA group, middle-dose MA group, and high-dose MA group) in a model of neurocognitive impairment induced by LPS (150 μg / 5 μL, 5 μL). IVIM-DWI sequence at 3.0T MRI; the scan time was 2 minutes and 17 seconds. The escape latency times of a Morris water maze test was used to evaluate the cognitive impairment rat model and the changes of learning ability of rats treated with different doses of MA (30 mg/kg, 60 mg/kg, 120 mg/kg). A GE postprocessing workstation (adw 4.5) was used to analyze the changes of each parameter (f value, D value, and D* value) in the IVIM data of each group. All the data were analyzed by one-way and two-way analysis of variance (ANOVA). The escape latency of the LPS group was significantly longer than the sham group (P = 0.05, 0.001, 0.006, and 0.042, respectively), and the high-dose group was significantly shorter than the LPS group on the sixth day (P = 0.034). Compared with the control group, the D values and f values of cerebral cortex and hippocampus were decreased significantly in the LPS group (P = 0.043 and 0.003; P = 0.029 and 0.016, respectively). With the increasing dose of MA, the D and f values of hippocampus and cortex increased, and there was a significant difference between the high-dose MA group and LPS group (D values: P = 0.038, 0.036; f values: P = 0.048, 0.039, respectively) DATA CONCLUSION: MA can improve the cognitive impairment induced by LPS by reducing neuroinflammation, and the changes of microcirculation and microperfusion in the brain tissue of these rats can be detected by IVIM imaging. 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1836-1843. © 2019 International Society for Magnetic Resonance in Medicine.