Dyslipidemia is one of risk factors for atherosclerosis induced by high fat diet. In atherosclerosis, an angiogenesis of immature and fragile vasa vasorum leads to atherosclerotic plaque destabilization. Angiogenesis of vasa vasorum is influence by oxidative stress and inflammation. Polysaccharide peptide (PsP) from Ganoderma lucidum (GL) contains bioactive compounds that possess antioxidant and anti-inflammatory properties which might become anti-angiogenesis agent in atherosclerosis. The aim of this study is to determine whether administration of PsP GL is able to decrease the number of vasa vasorum, H2O2 and Lp-PLA2 in atherosclerosis mouse model with dyslipidemia. True Experimental research design was conducted with Randomized Post Test Only Controlled Group Design. Twenty five Wistar strain Rattus novergicus were divided into 5 groups (n=5). Negative control group was administered with normal diet, positive control group was given high fat diet (HFD), and 3 treatment groups received HFD and PsP administration of 50mg/kgBW, 150 mg/kgBW, and 300mg/kgBW. Vasa vasorum measurement was performed using histopathological section of mouse aorta and measured using Scan Dot Slide Olyvia with 400x magnification. Serum Lp-PLA2 and H2O2 were measured using ELISA method. One way ANOVA analysis demonstrates that PsP GL significantly reduced vasa vasorum count (p<0,05) in mouse model of atherosclerosis with dyslipidemia. Duncan Post Hoc analysis indicates a significant difference in vasa vasorum count in 50mg/kgBW PsP treated group compared to other doses. The conclusions of this study is Polysaccharid peptide G. lucidum extract significantly reduces vasa vasorum count in Wistar strain Rattus novergicus with HFD administration.