The pneumatic compression system has demonstrated the potential to manage hypertrophic scar tissues using localized intermittent compressive forces. The underlying mechanism associated with these repeated, intermittent compressive forces is the remodeling capacity of collagen fibers of fibrous tissues in response to mechanical forces. Although intermittent compressive forces are clinically proven effective on managing hypertrophic scar, the optimal configurations of pressures and timing of intermittent compressive forces are largely unknown. In this study, we have developed a motor-driven ultrasound indentation system to apply programmable compressive forces and simultaneously assess soft tissue mechanical properties and responses. We further tested this system in various conditions with Institutional Review Board-approved protocols in human participants. The compressive force applied by the system was 40 mmHg on the skin of the forearm for 1 h with a frequency of 0.1 Hz. Soft tissue mechanical properties were assessed at three conditions, including (a) the forearm resting on the table with the wrist at a neutral position, (b) the forearm resting on the table with the wrist at 90° of extension or the maximal extension of the subject, and (c) forearm resting on the table with the hand holding a 1 kg weight. The effective Young’s modulus was calculated to characterize mechanical properties of forearm soft tissues. Before the 1 h intermittent compression treatment, effective Young’s modulus of conditions a, b, and c was 18.0, 11.3, and 16.8 kPa, respectively. After the treatment, the effective Young’s modulus of conditions a, b, and c was reduced by 13, 7, and 51%, respectively. The results support our general hypothesis that intermittent compression therapy may modulate soft tissue properties (e.g. hypertrophic scar). Future work should investigate the long-term effect of intermittent compression therapy on modulating soft tissue properties in patients with hypertrophic scars.