BACKGROUND: cAMP-response element binding protein (CREB) is a key modulator of various signaling pathways. CREB activation initiates a series of intracellular signaling pathways that promote neuronal survival. OBJECTIVE: To investigate the regulatory effects of basic fibroblast growth factor (bFGF) on cerebral neuronal CREB expression following ischemia/reperfusion injury. DESIGN, TIME AND SETTING: An immunohistochemical detection experiment was performed at the Department of Anatomy, Shenyang Medical College, between October 2006 and April 2008.MATERIALS: A total of 60 healthy, adult, Wistar rats were randomly divided into three groups: sham-operated (n=12), ischemia/reperfusion (n=24), and bFGF-treated (n=24). Rabbit anti-rat CREB (1: 100) and biotin labeled goat anti-rabbit IgG were purchased from the Wuhan Boster Company, China. MetaMorph-evolution MPS. 0-BX51 microscopy imaging system was provided by China Medical University, China. METHODS: Rat models of cerebral ischemia/reperfusion injury were developed using the suture method for right middle cerebral artery occlusion. Two-hour ischemia was followed by reperfusion. Rats from the bFGF-treated and ischemia/reperfusion groups were intraperitoneally administered endogenous bFGF (500 IU/mL, 2 000 IU/kg) or an equal amount of physiological saline. Rats from the sham-operated group underwent a similar surgical procedure, without induction of ischemia/reperfusion injury and drug administration. MAIN OUTCOME MEASURES: After 48-hour reperfusion, hippocampal and parietal cortical neuronal CREB expression was detected by immunohistochemistry, and the absorbance of hippocampal CREB-positive products was determined using MetaMorph-evolutionMP5.0-BX51 microscopy imaging system. RESULTS: The sham-operated group exhibited noticeable CREB expression in hippocampal and parietal cortical neurons. In the ischemia/reperfusion group, the CREB expression was discrete and neurons were poorly arranged. The bFGF-treated group exhibited increased CREB expression and better neuronal arrangement compared with the ischemia/reperfusion group. The mean absorbance of CREB-immunoreactive products in the hippocampus and parietal cortex was significantly higher in the ischemia/reperfusion group than in the sham-operated group (P＜0.05), and significantly higher in the bFGF-treated group than in the ischemia/reperfusion group (P＜0.05). CONCLUSION: bFGF significantly upregulates CREB expression in hippocampal and parietal cortical neurons following ischemia/reperfusion injury.