Through observing expression of cyclic AMP response element binding protein (CREB), and activity of MDA and SOD in Rats’ brains with cerebral ischemia, protective effects and the mechanism of traditional Yang-Tonifying Five-Returning Decoction and its ultra-micro preparation were brought to light. Methods:Model of cerebral ischemia was established. At Day 1 and Day 7, concentration of SOD and MDA were detected, and expressions of CREB were observed using immunohistochemical method by counting positive cells. Results:In ischemic brains, MDA increased while activity of SOD decreased markedly, suggesting the decoction was able to bring down MDA level and increase SOD activity, at the same time raise level of CREB to promote activation expression. The ultra-micro preparation with half dosage of crude drugs could reach the same effect as traditional decoction. With same dosage, the ultra-micro preparation was remarkably better than traditional decoction form. Conclusions:The ultra-micro preparation of compound Yang-Tonifying Five-Returning Decoction is better than traditional decoction at protecting cerebral ischemia caused brain injury in rats through bringing down MDA level, improving SOD activity, and promoting CREB activation.