To evaluate the clinical significance of nerve growth factor（NGF） in patients with cerebral small vessel disease（CVSD） and explore the relationship between NGF and the pathogenesis of depression after CVSD（CVSD-D）. Methods 80 Patients with first-onset CSVD were recruited. The CSVD were confirmed by MRI. Forty age and gender matched healthy people were selected as the control group. One month later，the diagnosis of post-stroke depression（PSD） was performed according to the American Classification and Diagnostic Criteria for Mental Disorders（DSM-IV）. Depressive symptoms are scored according to the 17-item Hamilton Depression Scale（HAMD-17 items）. The cubital venous blood was drawn within 24 hours after the depression scale was scored，and the serum NGF was detected by enzyme-linked immunosorbent assay（ELISA）. Results The serum NGF in patients with csvd were higher than those of normal patients，But in the CSVD patients，the serum NGF in patients with CSVD-D was lower than those of non CSVD-D group. The difference was statistically significant. Correlation analysis showed that there is no correlation between serum NGF and HAMD score（r=02096，P=0.3752）. Conclusion The occurrence of depression after cerebrovascular disease is closely related to the serum NGF level. But the degree of depression has no correlation with the NGF level.