The purpose of this study was to determine the feasibility and usefulness of contrast agent to detect internal bleeding. In a model of acute femoral artery injury, bleeding sites were produced percutaneously in 9 rabbits, using an 18 G needle guided by Doppler and B‐mode ultrasound. Imaging was performed pre‐ and post‐injury and after i.v. injection of contrast agent (Optison) using B‐mode, Color Doppler (CD), and Pulse Inversion. Gross and histological examination (light microscopy) of the injured blood vessel and the surrounding tissue were performed. Experiments with similar procedure were achieved in a pulsatile phantom with carotid arteries as targeted blood vessels in vitro. Bleeding sites could not be located in non‐contrast B‐mode sonography. After administration of contrast agent, injuries could be detected by the increased echogenicity of the extravasated blood flow. The resulted hematoma appeared as inhomogeneous hyper‐echo region. Color mosaic patterns were observed in the surrounding tissue with CD. Cluster of cavities were found within hematoma upon microscopy, which may be due to aggregated microbubbles. Bleeding sites were recognized in all contrast studies by CD; compared with only 11% in non‐contrast control. Contrast‐enhanced sonography is a promising tool in detection and evaluation of internal bleeding.