Abstract Body: Chronic, uncontrolled hypertension is a major risk factor for stroke leading to worse outcomes during acute stroke. Despite this, little is known how the biology of neural repair and post-stroke functional recovery are affected in hypertension. The goal of this study was to combine the photothrombotic model of stroke with a model of salt-sensitive hypertension to study the impact of hypertension on post-stroke motor recovery in mice. To induce hypertension, adult CD-1 male mice were placed on high-salt diet (0.9% NaCl solution) and implanted with deoxycorticosterone acetate (DOCA) pellet, whereas intact mice served as normotensive controls. Arterial blood pressure (BP) was monitored weekly via the tail-cuff method. At the end of week 3, elevation of mean arterial BP by ~27 mmHg was documented (p = 0.003). After confirming the elevated BP, the baseline motor function of the mice was evaluated in grid-walking and cylinder tests, followed by photothrombosis to induce stroke in the right sensorimotor cortex. The motor function was assessed additionally on post-stroke days 7, 14 and 21. Both hypertensive and normotensive mice exhibited a sustained functional deficit of the affected forelimb in grid walking and cylinder tests which was absent in the respective sham control animals (p = 0.002 compared to the respective baseline and sham group). Notably, the motor deficit was significantly more pronounced in the hypertensive animals (p = 0.001). To assess the capacity of functional recovery, hypertensive and normotensive mice were given overnight access to individual running wheels starting from post-stroke day 7, as a form of intense but delayed physical rehabilitation (6 days/week, until post-stroke day 21). Mice in both experimental groups covered a similar distance (p > 0.05) which plateaued at about 10 km of daily running by the end of the second week and lasted through the end of the study. Despite a similar rehabilitation dose, recovery of motor function appeared more pronounced in normotensive animals compared to hypertensive mice (p < 0.05). Our ongoing experiments are focused on the elucidation of the main molecular and cellular mechanisms of neural repair to further understand the impact of hypertension on post-stroke functional recovery. This study provides first-time evidence that photothrombosis in DOCA-salt model of hypertension could serve as a valuable model to study the impact of hypertension on neural repair and post-stroke functional recovery.