Interactions between bubbles and nearby boundaries have been studied for some time; however, the direct interactions between bubbles and tissue boundaries, especially blood vessel walls, have not been studied to a large extent. In this work high-speed microscopy was used to study the dynamical interaction between microbubbles and microvessels of ex vivo rat mesentery subjected to a single pulse of ultrasound. Ultrasound contrast agent microbubbles were injected into the blood vessels of rat mesentery subsequent to having the blood flushed out. India ink was used to increase the contrast between microvessels and surrounding tissues. Tissue samples were aligned at the focus of both an ultrasound transducer with a center frequency of 1 MHz and an inverted microscope coupled to a high speed camera. Fourteen high-speed microphotographic images were acquired for each experiment using 50 ns shutter speeds. Observations of the coupled dynamics between bubbles and vessels ranging from 10 μm to 100 μm diameters under the exposure of ultrasound of peak negative pressure within the range of 1 MPa to 7.8 MPa suggest that the vessel wall dilates during bubble expansion, and invaginates during bubble contraction. A significant finding is that the ratio of invagination to distension is usually >1 and large circumferential strains can be imposed on the vessel wall during vessel invagination. In addition, the surrounding tissue response was also quantified. Based on these studies, we hypothesize that vessel invagination is the dominant mechanism for the initial induction of vascular damage via cavitation.