The expression of c-Fos, an immediately early gene, is a marker of neural activity. In the present study, the effect of treadmill exercise on c-Fos expression was investigated in various regions of the rat hippocampus via immunohistochemistry. The first part of the experiment was aimed at determining the dependence of c-Fos expression on the intensity of treadmill exercise. In most of the hippocampal regions studied, increasing c-Fos expression was observed with increasing exercise intensity. In the second part of the experiment, the dependence of c-Fos expression on the duration of treadmill exercise was investigated. The c-Fos expression induced by mild-intensity exercise increased until the 7th day of exercise and subsequently decreased. Results of the present study suggest that the effect of treadmill exercise on neuronal activity in the hippocampus is intensity-and duration-dependent.