Recent studies have shown that the adventitia contains arterial progenitor cells expressing the stem cell antigen-1 marker (Sca-1). These Sca-1+ cells function as stem/progenitor cells that have been reported to transform into smooth muscle cells and promote neo-intimal formation. We have previously found a striking deposition of adventitial collagen in the setting of experimental hypertension in mice. This fibrotic layer of collagen contributes to aortic stiffening and potentially loss of the windkessel effect, promoting systolic hypertension. Because collagen deposition occurs at the site of Sca1+ cells, we therefore hypothesized that Sca-1+ progenitor cells might serve as a source of adventitial collagen. Using confocal microscopy, we first found a dramatic increase of Sca-1+ cells in angiotensin II-treated vessels in the advential and peri-adventitial region, with no increase in CD68+ cells. These Sca-1+ cells represented approximately one fourth of total adventitial cells. Flow cytometry indicated that Sca-1+CD31- cells were tripled in the aortas of angiotensin II-treated mice (5.6±1.6 ×103 vs. 15.9±2.4 ×103 cells/per aorta sham vs. angiotensin II, p<0.05). We then isolated aortic Sca-1+ cells in sham and angiotensin II-treated mice using magnetic-activated cell sorting (MACS) and found collagen 1a1 gene was upregulated more than 7 fold in these cells (0.94±0.17 vs. 7.27±1.22, sham vs. angiotensin II, p<0.01). In addition, we did not see any obvious microvessel staining for Sca-1 in the adventitia, indicating these cells did not arise from the vasa vasorum. In summary, resident Sca-1+ progenitor cells likely contribute to adventitial collagen deposition and promote angiotensin II-induced aortic stiffening.