Exercise increases adult hippocampal neurogenesis (AHN) and enhances memory function. To elucidate optimal exercise, especially exercise intensity, on hippocampus-based cognition, we established treadmill running animal model, in which running speed was defined using the blood lactate threshold (LT). Using this exercise model, we found for the first time that hippocampal neurons were activated after acute mild exercise (ME) below the LT with running stress minimized. In addition, chronic ME enhanced AHN and spatial memory function. We review the beneficial effects of ME and discuss several molecular factors underlying ME-enhanced hippocampal function.