Changes in the ultrastructure of vascular tissue due to pathologies such as atherosclerosis may be manifested as subtle changes in the mechanical properties of the arterial wall. The ability to detect these changes is considered to be important in the early diagnosis of atherosclerosis. In order to evaluate the subtle viscoelastic properties of the arterial wall, a highly sensitive means of evaluating mechanical strain in the tissue is required. Herein we will present a novel laser speckle strain gauge for evaluating mechanical microstrains in perfused and superfused vessel segments. The strain gauge relies upon 2D frequency transforms of stacked speckle histories, which are time sequences of one dimensional views of the backscattered light stacked into a 2D array such that time is along the vertical axis and space is along the horizontal axis. The gauge can be made sensitive only to in-plane strains. Sensitivity of the gauge is on the order of single microstrain. By mechanically straining the vessel segments in a custom microtensile testing machine fitted with a high sensitivity load cell, mechanical constants of the vessel wall can be derived and changes in the mechanical behavior due to disease can be evaluated.