A real‐time temperature/strain imaging system for monitoring HIFU‐induced lesions was implemented in conjunction with a pulsed HIFU (pHIFU) phased array driver. The integrated system is capable of collecting two‐dimensional (2D) strain/temperature fields at high frame rates (>200 fps) to capture intricate tissue motions and deformations in the vicinity of the pHIFU focus. In addition, the system is capable of refocusing and updating the pHIFU beam at rates up to 1000 times per second. These capabilities of the guidance and pHIFU control allow for precise lesion formation in the presence of tissue motion and deformation due to breathing and pulsation in the vicinity of large blood vessels. We present results from in vivo experiments in the hind limbs of Copenhagen rats (250 g average). The results demonstrate the capability of the strain imaging system to estimate the thermally induced strain (due to pHIFU) in the presence of high strains from breathing and vessel pulsation in vivo. In this paper, we describe the architecture and the signal processing algorithms used in the estimation of pHIFU‐induced strains. The robustness of the method will be illustrated by describing the results from the application of pHIFU beams in close proximity to femoral artery of the rat model.