Objective: To explore the histopathology, monocytes phenotypes and brain mRNA transcription of angiogenic and atherogenic factors preliminarily in spontaneous hypertensive rats (SHRs) fed with high salt diet and subjected to chronic focal hypoperfusion. Methods: A total of 21 SHRs were randomly assigned into SHR with normal diet (SHR-ND group, n=7), SHR fed with high salt (8%) chows (SHR-HSD group, n=14) groups. After induction of high salt diet for 20 weeks, unilateral carotid artery occlusion was applied to one half of SHR-HSD (SHR-HSD-UCAO, n=7) group for 10 weeks to mimic chronic focal cerebral hypoperfusion. The neuropathology, monocytes phenotypes and brain transcription of fibroblast growth factor (FGF-b), platelet-derived endothelial cell growth factor (PD-ECGF), angiogenin (ANG), transforming growth factor-β (TGF-β) and vascular endothelial growth factor A (VEGF-A) among three groups were compared. Results: The systolic blood pressure ((246±12) mmHg vs (220±16) mmHg, P=0.0291, 1 mmHg=0.133 kPa) and diastolic blood pressure ((189±15) mmHg vs (164±12) mmHg, P=0.0143) of SHR-HSD group were elevated significantly compared with those of SHR-ND group. Compared with normotensive Wistar-Kyoto (WKY), SHR-ND, SHR-HSD and SHR-HSD-UCAO groups demonstrated lipohyalinosis, vessel wall thickening, lumen narrowing and multiple enlarged perivascular space and diffuse disarrangement of nerve fiber and myelin vacuolation in corpus callosum pathologically. The ratio of CD11b(+) CD68(+) monocytes in peripheral blood of SHR-HSD group was higher compared with both SHR-ND and SHR-HSD-UCAO groups (P=0.000 8). The mean inflorescence index (MFI) of CD86 and CD206 showd considerable decline in SHR-HSD-UCAO group compared with those of SHR-HSD group (P=0.018 7 and 0.016 8, respectively). The CD86 MFI of CD11b+CD68+ monocytes in SHR-HSD-UCAO group was remarkably higher than that of SHR-ND and SHR-HSD groups (P=0.000 5). Compared with SHR-ND and SHR-HSD groups, the brain mRNA transcription of angiogenic factors including PD-ECGF and ANG were down-regulated (P=0.004 6 and 0.000 2, respectively), while the atherogenic factors including TGF-β and VEGF-A were up-regulated in SHR-HSD-UCAO group (P<0.000 1 and P=0.045, respectively). Conclusion: SHR-HSD-UCAO group shares the pathophysiological characteristics with advanced stage arteriosclerotic cerebral small vessel disease (aCSVD), including neuropathology, imbalanced circulating monocytes phenotypes and down-regulated angiogenic factors.