Experimental studies using laboratory animal models have shown a potential vasoactive effect of natural metabolites such as glycine. The present study used intravital microscopy in laboratory rat models to study the microcirculation in the brain pial and mesentery vessels. To investigate the pial microvasculature, a stereotaxis-like animal fixing device was used. The intravital microscopy unit consisted of a binocular microscope equipped with a digital photo-video camera, processor, monitor and printer. Using reflected light, a special contact lens with an amplified focus depth provided high-resolution images of nontransparent tissue objects that typically have insufficient light exposure. Glycine had a vasodilatory effect on microvessels in the rat brain and mesenterium. The diameter of pial arterioles increased after glycine application especially markedly (up to 250% of initial size). These changes were not observed when physiological saline was used. Even a very small amount of glycine (a drop on the needle) was sufficient to stop the early stages of histamine-induced blood stasis development in 3-5 s in mesenterial microvessels. The vasodilatory effect of glycine on the pial microcirculation correlates with its reported positive therapeutic effect in cerebral ischemic stroke. The ability of glycine to avoid or prevent histamine-induced microcirculatory alterations in mesenterial microvessels may have potential clinical applications.