This dataset contains MALDI-MSI (Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging) metabolomics data acquired from aortic root sections in an atherosclerosis regression experiment designed to study lesional macrophage metabolism in the context of efferocytosis. Ldlr−/− mice were fed a Western-type diet for 16 weeks to establish advanced atherosclerotic plaques, after which a subset was switched to a chow diet and treated with an adeno-LDLR construct to induce plaque regression. The dataset focuses on MALDI spectra acquired from aortic root lesions at 2 and 5 weeks of regression. Week 2: 16,809 spectra, 8,000 spectral data points, m/z range ~10.00–1002.88. Week 5: 18,676 spectra, 8,000 spectral data points, m/z range ~10.00–1020.39. Spectra were acquired in raw profile mode with background pixels removed. The uploaded data represents the global mean spectrum for each time point, averaged across all individual spatial spectra. This dataset was used in the development and validation of the GALAxY (peak Group ALignment of mAss spectrometrY data) algorithm.