In experimental stroke research, anesthesia is common and serves as a major reason for translational failure. Real-time cerebral blood flow (CBF) monitoring during stroke onset can provide important information for the prediction of brain injury; however, this is difficult to achieve in clinical practice due to various technical problems. We created a photothrombotic focal ischemic stroke model utilizing our self-developed miniature headstage in conscious and freely moving rats. In this model, a high spatiotemporal resolution imager using laser speckle contrast imaging technology was integrated to acquire real-time two-dimensional CBF information during thrombosis. The feasibility, stability, and reliability of the system were tested in terms of CBF, behavior, and T2-weighted magnetic resonance imaging (MRI) findings. After completion of occlusion, the CBF in the targeted cortex of the stroke group was reduced to 16 ± 9% of the baseline value. The mean infarct volume measured by MRI 24 h postmodeling was 77 ± 11 mm3 and correlated well with CBF (R2 = 0.74). This rodent model of focal cerebral ischemia and real-time blood flow imaging opens the possibility of performing various fundamental and translational studies on stroke without the influence of anesthetics.