Objective---This study investigated the effects of rosuvastatin on plaque progression and in vivo coronary artery function in apolipoprotein E knockout (ApoE KO) mice, using non-invasive high-resolution ultrasound techniques. Methods and Results---Eight-week-old male ApoE KO mice (n=20) were fed a high-fat diet with or without rosuvastatin (10 µmol/kg/day) for 16 weeks. Compared to control, rosuvastatin reduced total cholesterol levels (P<0.05) and caused significant retardation of lesion progression in the brachiocephalic artery, as visualized in vivo using an ultrasound biomicroscope (P<0.05). Histological analysis confirmed the reduction of brachiocephalic atherosclerosis and also revealed an increase in collagen content in the statin-treated group (P<0.05). Coronary volumetric flow was measured by simultaneous recording of Doppler velocity signals and left coronary artery (LCA) morphology before and during adenosine infusion. The hyperemic flow in response to adenosine was significantly greater in LCA following 16 weeks of rosuvastatin treatment (P<0.001), while the baseline flow was similar in both groups. Conclusions---Rosuvastatin reduced brachiocephalic artery atherosclerotic plaques in ApoE KO mice. Coronary artery function assessed using recently developed in vivo ultrasound-based protocols, also improved.