This study demonstrates that circulating CD45+Col I+CXCR4+ fibrocytes contribute to the pathogenesis of pulmonary fibrosis. Fibrocytes, a minor component of peripheral blood leukocytes, express collagen I and CD45 and migrate in response to CXCL12. In a murine model of bleomycin-induced pulmonary fibrosis, these fibrocytes were found to traffic to the lungs and correlate with increased collagen deposition. Treatment with neutralizing anti-CXCL12 antibodies inhibited the recruitment of fibrocytes and attenuated lung fibrosis. These findings suggest that circulating fibrocytes play a significant role in the development of pulmonary fibrosis and may represent a novel therapeutic target.This study demonstrates that circulating CD45+Col I+CXCR4+ fibrocytes contribute to the pathogenesis of pulmonary fibrosis. Fibrocytes, a minor component of peripheral blood leukocytes, express collagen I and CD45 and migrate in response to CXCL12. In a murine model of bleomycin-induced pulmonary fibrosis, these fibrocytes were found to traffic to the lungs and correlate with increased collagen deposition. Treatment with neutralizing anti-CXCL12 antibodies inhibited the recruitment of fibrocytes and attenuated lung fibrosis. These findings suggest that circulating fibrocytes play a significant role in the development of pulmonary fibrosis and may represent a novel therapeutic target.