The lymphatic vessels act as the immune systems highway yet we know little about the variation in cells entering the lymphatics in response to immune stimuli as they are difficult to access in rodent models. We have directly cannulated the afferent and efferent lymphatic vessels in sheep to quantify the kinetics, composition and maturation of innate immune cell types over time in response to a number of common classes of vaccine adjuvants. We show that vaccine adjuvants have highly differential effects on antigen transport, cellular maturation and phagocytic capability which correlate with enhanced antigen specific immunity. We have quantified the real time in vivo kinetics of cells draining a vaccination site in response to liposome, oil and aluminium hydroxide based delivery systems containing innate immune stimulators. This is in a large animal where the dose and volume of vaccine administered is very similar to that used in humans.