The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) in preventing joint stiffness. Unilateral knee joints were immobilized in two groups of rats (n = 6/period/getup). Under general anesthesia, the immobilized knee joints were exposed to LIPUS for 20 min/d, 5 d/wk, using an existing LIPUS device (LIPUS group, 1.5-MHz frequency, 1.0-kHz repetition cycle, 200-mu s burst width and 30-mW/cm(2) power output) until endpoints (2, 4 or 6 wk). In the control group, general anesthesia alone was administered in the same manner as in the other group. The variables compared between the groups included joint angles; histologic, histomorphometric and immunohistochemical analyses; quantitative reverse transcription polymerase chain reactions; and tissue elasticity. LIPUS had a preventive effect on joint stiffness, resulting in decreased adhesion, fibrosis and inflammation and hypoxic response after joint immobilization. (C) 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.