Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which. The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment. Display omitted •Developing candesartan-liposomes containing ethanol and propylene glycol (CLEP) could improve its release and permeation.•The study aimed to develop a nasal CLEP formulation as a potential diabetes-associated stroke treatment.•The optimum CLEP formulation significantly increased the release and permeation of candesartan relative to free candesartan.•The optimum CLEP formulation reduced the infarction after stroke in rats and enhanced grip strength.•The optimum CLEP formulation decreased flexion, spontaneous motor activity, and time spent in the target quadrant.