Objective The purpose of this study is to understand the function of Fkbp51 in metabolic pathways and neural pathways by profiling gene expression of liver and hippocampus tissues of both Fkbp51KO and WT mice.Methods mRNAs of liver and hippocampus of Fkbp51KO and WT mice were isolated and expression profiling was performed using RNA-seq. Differentially expressed gene between KO and WT were analyzed using BRB-Array Tools. DAVID, STRING, Genecard programs, the Gene Ontology, the Protein-protein Interaction Network and the Gene Annotation were applied to identify significant functional-relevant pathways. Results When compared differentially expressed genes between Fkbp51KO and WT in liver, we found that the loss of Fkbp51 in liver has large effect on the genes related to steroid biosynthetic and metabolic process, lipid biosynthetic process and oxidation reduction. When differentially expressed gene in hippocampus was studied between genotypes, we found that elimination of Fkbp51 has much effect on genes related to detection of mechanical stimulus, learning or memory, regulation of synaptic transmission and the pathway of PPAR and amyotrophic lateral sclerosis (ALS) e.g. When intersection of gene lists between liver and hippocampus tissues, we identified 11 common differentially expression genes. In these genes, HMGCS2 and INSIG1 are grouped in one protein-protein interaction network, and USP2, PER, CRY and DBP are grouped in another network. Conclusions The role of Fkbp51 in metabolism and nervous system is not only independent but also interactive.