The mechanisms of high-altitude adaption in Glyptosternum maculatum, an endemic fish from the Tibet Plateau, further provides a foundation for investigation. In this paper, the mechanism of metabolic differences between the liver and exo-celiac liver of G. maculatum was studied by histological and biochemical methods and Transcriptomics. The results showed that there were no significant differences in the structure, the number of mitochondria, and the protein composition of mitochondria between the liver and exo-celiac liver. A total of 138,515 unigenes with an average length of 814 bp were obtained from the two tissues. Compared with the liver, 45 upregulated genes and 32 down-regulated genes were detected in the exo-celiac liver. Through GO analysis, DEGs such as Hmgcl, Tbxas1, Cask, Sumf1, Jak1, and Glxk, which are involved in amino acid and fatty acid metabolism, were screened out. KEGG analysis showed different expression genes enriched in butanoate and tryptophan metabolism, peroxisome, valine, leucine, lysine, and isoleucine degradation, and other metabolic pathways. Four differential expression genes were selected for qRT-PCR detection. It was found that the results of qRT-PCR were consistent with the sequencing results of the transcription group. In conclusion, there are differences between amino acid, fatty acid, and energy metabolism between the liver and exo-celiac liver of G. maculatum. The mechanisms may be related to the significant differential expression of Hmgcl, Ptk2b, Gba, and Dnm1l genes in the liver and exo-celiac liver. In this study, we screened the key genes and signaling pathways that regulate liver metabolism mechanisms in G. maculatum, which laid a theoretical foundation for revealing the different metabolic mechanisms between the liver and exo-celiac liver of G. maculatum.