This randomized, double-blind, parallel-design study compared the short-term effects of rosuvastatin and atorvastatin on serum lipids and markers of inflammation and endothelial function in patients with stable atherosclerosis. Patients received either 10 mg/day rosuvastatin (n = 18) or 20 mg/day atorvastatin (n = 18), orally, for 4 weeks. Serum lipids, high-sensitivity Creactive protein (hsCRP), Rho-associated coiled-coil containing protein kinase (ROCK) activity and flow-mediated dilation (FMD) of the brachial artery were assessed before and after therapy. Both statins produced significant reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and hsCRP levels, and significant increases in FMD. Both statins significantly reduced ROCK activity and inhibition was significantly greater with rosuvastatin. There was no correlation between ROCK activity and LDL-C level in either group. There was a significant correlation between ROCK activity and FMD for both statins, but no correlations between FMD and LDL-C or hsCRP levels. Short-term treatment with either rosuvastatin or atorvastatin inhibits ROCK activity independent of cholesterol reduction, and improves endothelium dysfunction in patients with atherosclerosis.