The study aims to explore the protection mechanism of exogenous basic fibroblast growth factor (exo-bFGF) in brain ischemia. The first part of experiment was to determine the optimal time window for the permeation of exo-bFGF through damaged blood-brain barrier in rats with permanently occluded middle cerebral arteries. 125I labeled bFGF was administered to the rats through the caudal vein. The level of gamma-rays of 125I-bFGF in the ischemic brain were found to increase at 2 h and a high level was maintained for 14 days. The morphology of the basement membrane of capillaries was observed using anti-blood-brain barrier basement membrane glycoprotein immunohistochemistry. The normal continuous linear or ribbon-like immunostain of the basement membrane became granular at 0.5 h, gradually faint and finally negative. The newly formed capillaries at the edge of the infarct still showed a negative stain after 14 days. The result suggested the optimal time window of exo-bFGF began 2 h after insult. The second part of experiment was to observe the dynamic expression of early growth response protein (Egr-1), endogenous basic fibroblast growth factor (endo-bFGF) and bFGF receptor (bFGFR) using immunohistochemistry after exo-bFGF is administered to brain. Egr-1 was more significantly enhanced in the exo-bFGF-used group than in the control group. Endo-bFGF increased gradually, reaching its peak at 7 days in the control group, while in experiment group, the endo-bFGF expression showed its first peak at 6 h, indicating that exo-bFGF could induce earlier and stronger expression of endo-bFGF. The bFGFR-group presented an early expression, reaching its maximal level at 3 h, and declining at 6 h. There were no difference in expression of bFGFR between the two groups. The infarct areas reduced from 17% to 24% in the different time intervals. The results suggested that in exo-bFGF enhanced Egr-1 protein. Egr-1 in turn might play an important role in up-regulating the expression of endo-bFGF which overlapped with the expression of bFGFR to ensure the combination of ligand and receptor to protect against brain ischemia.