Introduction Ketamine‐induced cystitis (KIC) is a disease caused by ketamine that can cause lower urinary tract symptoms (LUTS). Its end‐stage is bladder contracture, which is related to bladder fibrosis and poses a serious burden to patient lives. Methods We established a KIC model in female Sprague Dawley rats and verified bladder fibrosis in the model by Masson trichrome staining and western blot analysis. The bladders of the rats from the ketamine and control groups were used to perform transcriptome analysis. In particular, association analysis with metabolomics was also used to determine the potential mechanisms of ketamine‐induced bladder fibrosis. Results A total of 685 differentially expressed messenger RNAs, 71 differentially expressed long noncoding RNAs, 23 differentially expressed microRNAs, and 68 differentially expressed circular RNAs were identified. We found that ribosome, Wnt signaling, vascular endothelial growth factor signaling, cytoskeleton organization, and cytoskeletal protein binding may be potential pathways in ketamine‐induced bladder fibrosis as identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. In addition, the mitogen‐activated protein kinase pathway appeared to be closely related to the development of ketamine‐induced bladder fibrosis according to association analysis. Conclusions In this study, using transcriptomic and correlation analyses of metabolomics, we identified pathways that may be potential targets for the prevention and treatment of ketamine‐induced bladder fibrosis.