Objective：To observe the protective effect of nerve growth factor（NGF） loaded ploy lactic-co-glycolic acid（PLGA） micro－spheres on retinal ganglion cells（RGCs） following the optic nerve injury. Methods：The NGF-PLGA microspheres were made using PLGA and the properties of microspheres were tested. Totally 69 SD adult male rats were randomly divided into 5 groups：normal control group（group A），sham operated group（group B），physiological saline injection group（group C），NGF injection group（group D） and NGF-PLGA injection group（group E）. Nine rats in groups A and B，17 rats in groups C，D and E. All rats in groups B-E underwent ultrasound irradiation. Samples of retinal section were collected for immunohistochemistry staining and HE staining to ob－serve the performance of glucose regulated protein 78 kD（GRP78） and the pathological morphology change of retina of each group at 12 h and on the 1st d，3rd d，7th d. Number of RGCs retrograde labeled by fluorogold（FG） before the operation was checked on the 7th d. Results：The mean size of microsheres was （3.17±0.60） μm. The encapsulation efficiency of NGF-PLGA microspheres was 68.4%，the loading rate was 0.0323% and the cumulative rate of drug-release on the 7th d was 82.6%.There were significant differ－ences among 5 groups in RGCs count（F=65.858，P=0.000）.There was no difference in RGCs count between group A and B（P=0.862>0.05），but apparent differences among other groups were observed（P<0.05）. Imunohistochemistry staining showed no positive cell in groups A or B. There were significant differences in GRP78 positive rate of RGCs among groups C-E at different time points（Fgroup=184.330，Pgroup=0.000） and among each group at different time points（Ftime=21.472，Ptime=0.000）. HE staining showed the retinal ede－ma of group E was reduced on the 7th d compared with that of group C and D. Conclusion：NGF loaded PLGA microspheres com－bined with ultrasonic irradiation can improve the protective ef－fect on RGCs after the optic nerve injury.