Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway. Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham, model and low/mid/high concentration lycopene groups. Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in rats were detected using echocardiography, creatine kinase (CK), lactate dehydrogenase (LDH), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) were detected using ELISA, matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and PI3K/Akt pathway related protein expression were detected using Western blot, and liver X receptor α (LXRα) and liver X receptor β (LXRβ) expression were detected using immunohistochemical staining. In vitro, a hypoxia model of myocardial microvascular endothelial cells (MCMEC) was established, with groups including control, hypoxia, hypoxia＋low/mid/high concentration lycopene, LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group. Cell viability was detected using CCK-8, LXRα and LXRβ were detected using immunofluorescence, superoxide dismutase (SOD), reactive oxygen species (ROS), VEGF and PDGF levels were detected using ELISA, mitochondrial function-related proteins (Drp1, Fis1, LC3-II/LC3-I, PINK1, Parkin and Opa1) and MMP-9, MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot, and myocardial tissue injury was evaluated using HE staining. Results Compared with the sham group, the model group exhibited severe myocardial injury, with increased levels of LVEDD, LVESD, CK and LDH, decreased LVEF and LVFS, downregulated expression of VEGF, PDGF, MMP-9 and MMP-2, decreased expression of p-PI3K/PI3K and p-Akt/Akt, and downregulated expression of LXRα and LXRβ. In cells, compared with the control group, the hypoxia group showed decreased cell viability, downregulated expression of VEGF, PDGF, MMP-9, and MMP-2, and decreased expression of p-PI3K/PI3K and p-Akt/Akt. Lycopene treatment could effectively reverse the above changes and increase the expression of LXRα and LXRβ. Moreover, lycopene could also reverse and modulate the characteristic alterations of Drp1, Fis1, LC3-II/LC3-I, PINK1, Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors. Conclusion Lycopene enhances mitochondrial activity, reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.