Infection-induced inflammation is a major cause of injury to the white matter and grey matter structures of the brain in the early preterm infant. Rodent models of neonatal inflammatory brain injury commonly utilize bacteria-derived lipopolysaccharide (LPS) exposure in new-born pups, which exhibit a similar timing of neuronal and oligodendroglial development to the very preterm infant. In the present study, we assessed the long-term effects of early-life inflammation on white and grey matter microstructure using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) at 9.4T.Sprague-Dawley rats received repeated intraperitoneal injection of low-dose LPS (300 mg/kg; LPS group, n=9) or saline (CT group, n=9) once daily from postnatal (P) days 1 to 3. At P21 rats were sacrificed and brains were formalin-fixed for subsequent histology and ex-vivo MRI. MR experiments were performed on an actively-shielded 9.4T/31cm magnet (Agilent) equipped with 12-cm gradient coils (400mT/m, 120µs) with a 2.5 mm diameter birdcage coil. A multi-b-value shell protocol was acquired using a spin-echo sequence with the following parameters: FOV = 21×16 mm², matrix size = 128×92, 12 slices of 0.6 mm thickness in the axial plane, 3 averages with TE/TR = 45/2000 ms. A total of 96 diffusion weighted images were acquired, 15 of them as b₀ reference images. The remaining 81 were separated in 3 shells with the following distribution (# of directions/b-value in s/mm²): 21/1750, 30/3400 and 30/5100. All 81 directions were non-collinear and were uniformly distributed in each shell. The total acquisition time was 15h per brain. Acquired data were fitted using the NODDI toolbox [2]. The diffusion tensor (DT) was spatially normalized to the study-specific DT template using DTI-TK [3]. The regions of interest (ROI) were drawn on the DT study-specific template and were then transformed back to the subject space in order to compute ROI-averaged estimates of DTI and NODDI maps. Six different brain regions were identified on the DT-template: cortex (Cx), corpus callosum (CC), internal capsule (IC), external capsule (EC), cingulum (Cg) and Striatum (St). For statistics (LPS vs. CT), a Mann Whitney test was used (significance: *P<0.05)No overt trace of ventriculomegaly was observed. In the white matter, there was no significant change observed between the groups in the CC and Cg, except for a trend (P=0.05) of increased ODI in the CC in LPS rats. There was a significant decrease in FA and increase in ODI in the IC and EC in LPS rats. There was also a significant increase in ficvf in the EC and an increase in fiso in the IC in LPS rats compared to controls. By contrast, in the cerebral cortex there was a significant increase in FA and decrease in ODI in LPS rats compared to controls.In this study, we characterized the microstructural consequences of LPS exposure in newborn pup rats recovered to P21. Mild changes in white matter and cortical development were observed without ventriculomegaly. Cortical structure was abnormally developed with potential growth retardation in dendritic arborization (leading to increased FA and decreased ODI). Although there was only a small effect on the CC (ODI increased) tracts, results from the EC and IC were suggestive of myelination impairment, as characterized by a decrease in FA and increase in ODI (fiber compaction defect) and an increase in ficvf (potential cytotoxic edema) in the EC, and an increase in fiso (potential vasogenic edema) in the IC. In conclusion, DTI and NODDI can be used to assess subtle changes in cerebral impairment following LPS exposure. These techniques may be of high interest for the clinical community of neonatologists due to their translational utility.