Backgraound: Berberine (BBR) is a plant alkaloid which possesses anti-inflammatory and anti-oxidant effects with low oral bioavailability. In this study, micelle formulation of BBR was investigated in order to improve therapeutic efficacy and examined its effect on secretion of inflammatory cytokines in cerebral ischemia in animal model. Material and Methods: Nano formulation was prepared by thin film hydration method, and characterized by particle size, zeta potential, morphology, encapsulation efficacy and drug release in Simulated Gastric Fluid (SGF) and Simulated Intestine Fluid (SIF). Then, rats were pretreated with drug (100 mg/kg) and nano drug (25, 50, 75, 100 mg/kg) for 14 days. Stroke induction was accomplished by Bilateral Common Carotid Artery Occlusion (BCCAO), TNF-α, IL-1ß, and MDA levels were measured in the brain and the anti-inflammatory effect of BBR formulations were examined. Result and discussion: Micelles were successfully formed with appropriate characteristics and smaller sizes than 20 nm. The PDI, zeta potential, encapsulation efficacy of micelles were 0.227, -22 mV, 81%, respectively. Also, the stability of nano micelles was higher in SGF as compared to SIF. Conclusion: Our clinical data show that treated groups in different doses (nano BBR 100, 75, 50 mg/kg, and BBR 100 mg/kg) successfully showed decreased levels of the inflammatory factors in cerebral ischemia compared with stroke group and treated group with nano BBR in dose of 25 mg/kg. Nano BBR formulation with lower dose can be a better candidate than conventional BBR formulation to reduce oxidative and inflammatory factors in cerebral ischemia.