With the increasing number of transgenic mouse models of human brain diseases, there is a need for a sensitive method that allows assessing quantitative whole brain perfusion within a reasonable scan time. Arterial spin labeling (ASL), an MRI technique that permits the noninvasive quantification of cerebral blood flow, has been used to assess rodents brain perfusion. For mice, the reported experiments performed with continuous or pulsed ASL were challenged by poor multislice capability, limited sensitivity, or quantification issues. Here, the recently proposed pseudo‐continuous ASL strategy, which has shown great promise for human studies, was investigated for mouse brain perfusion imaging at 11.75 T. Pseudo‐continuous ASL was experimentally optimized and compared with a standard flow‐sensitive alternating inversion recovery sequence for sensitivity, robustness, absolute quantification, and multislice imaging capability. A sensitivity gain up to 40% and clear advantages for multislice imaging are obtained with pseudo‐continuous ASL. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.