Several studies show that prostatic fibrosis is associated with male lower urinary tract dysfunction (LUTD). Development of fibrosis is typically attributed to signaling through the TGFβ pathway, but our laboratory has demonstrated that in vitro treatment of human prostatic fibroblasts with the CXCL12 chemokine stimulates myofibroblast phenoconversion, and that CXCL12 has the capacity to activate profibrotic pathways in these cells in a TGFβ-independent manner. We have previously reported that feeding mice a high fat diet (HFD) results in obesity, II diabetes, increased prostatic fibrosis, and urinary voiding dysfunction. The purpose of this study was to test the hypothesis that in vivo blockade of the CXCL12/CXCR4 axis would inhibit the development of fibrosis-mediated LUTD in HFD fed mice.