Schistosomiasis is a parasitic disease that imposes a significant burden on society. The eggs are the primary pathogenic factor in schistosomiasis, and their accumulation in liver could lead to the formation of granulomas and liver fibrosis. However, the metabolic changes in liver resulting from schistosomiasis remain poorly understood. We established a mouse model of schistosomiasis japonica, where the eggs accumulate in the liver and form egg granulomas. We used mass spectrometry imaging to analyze the differences in metabolites among various liver regions, including the liver tissue from normal mice, the liver area outside the granulomas in schistosomiasis mice, and the granuloma region in schistosomiasis mice. There were significant differences in metabolites between different liver regions, which enriched in metabolic pathways such as the biosynthesis of unsaturated fatty acids, taurine and hypotaurine metabolism, glycerophospholipid metabolism, glycolysis/gluconeogenesis, purine metabolism, arachidonic acid metabolism, and bile secretion. In normal liver tissue, higher concentrations of oleic acid (FA (18:1)), eicosapentaenoic acid (FA (20:5)), and L-glutamine were observed. In liver regions outside the granulomas, D-glucose and pyruvic acid were elevated compared to those in normal mice. Taurine increased in the liver of schistosomiasis. Meanwhile, there were elevated uric acid and spermidine in the egg granulomas. We employed mass spectrometry imaging technology to investigate metabolic reprogramming in liver of Schistosoma japonicum-infected mice. We explored the spatial distribution of differential metabolites in liver of schistosomiasis including unsaturated fatty acids, taurine, glutamine, spermidine, and uric acid. Our research provides valuable insights for further elucidating metabolic reprogramming in schistosomiasis.