Objective  To investigate the optimal time and mechanism of nerve growth factor（NGF）crossing the bloodbrain barrier (BBB) under cerebral ischemia in rats through focal cerebral ischemia experiments in rats, and to provide a new way for the clinical application of NGF.   Methods  A total of 65 healthy Sprague-Dawlay (SD) male rats were prepared by using a modified suture method  to prepare focal cerebral ischemia models. Rats were injected with 125Ⅰ-NGF, and the γ count was measured with a γ-ray counter to observe the changes in BBB permeability at different times of ischemia. At the time point at which BBB permeability was greatest after cerebral ischemia (3 days ischemia), the rats were used as the experimental group (n=15). Coronal sections of the rats were subjected to autoradiography, and the imaging site, area and brightness were observed. The changes of blood-brain barrier at different times of cerebral ischemia with transmission electron microscope were observed.   Results  With the prolongation of cerebral ischemia time, the permeability of BBB increased gradually, and the permeability of BBB was the largest after 3 days of cerebral ischemia, and then weakened gradually. With the same permeability of BBB, the γ count showed that the γ counts of the control group and the experimental group increased with the prolonged medication time. The γ counts of the experimental group at each time point were higher than the control group. Significant difference (P<0.05) was found, and the highest γ count at 4 hours. The result  of autoradiography showed that the entire brain was not developed in the control group for 1 hour, and the ventricles and periventricular brain tissues were developed in 4 hours and 7 hours. The area occupied about 4.1% of the cerebral coronal section, and the brightness was obvious. The area was about 6% of the coronal section of the brain, and the brightness was strong. In addition to the development of the ventricles and periventricular brain tissues at 4 hours and 7 hours, in the right frontal lobe (FL), parietal lobe (AL) and temporal lobe, there was a large area in the medulla and the medulla, which covered 36.2% to 47.3% of the coronal section of the brain. The brightness was very strong.   Conclusion  BBB permeability increases with prolonged cerebral ischemia in rats, of which the permeability is the strongest at 3 days of ischemia; rats with focal cerebral ischemia at 3 days for 4 hours, 125Ⅰ-NGF enters the BBB in the largest amount, in the frontal and parietal. The temporal lobe is most obvious. NGF can pass the blood-brain barrier of focal cerebral ischemia and may become a new breakthrough in clinical drug delivery.