Aerobic exercise has been well established to promote enhanced learning and memory in both human and non-human animals. Exercise regimens enhance blood perfusion, neo-vascularization, and neurogenesis in nervous system structures associated with learning and memory. The impact of specific plastic changes to learning and memory performance in exercising animals are not well understood. The current experiment was designed to investigate the contributions of angiogenesis and neurogenesis to learning and memory performance by pharmacologically blocking each process in separate groups of exercising animals prior to visual spatial memory assessment. Results from our experiment indicate that angiogenesis is an important component of learning as animals receiving an angiogenesis inhibitor exhibit retarded Morris water maze (MWM) acquisition. Interestingly, our results also revealed that neurogenesis inhibition improves learning and memory performance in the MWM. Animals that received the neurogenesis inhibitor displayed the best overall MWM performance. These results point to the importance of vascular plasticity in learning and memory function and provide empirical evidence to support the use of manipulations that enhance vascular plasticity to improve cognitive function and protect against natural cognitive decline.