The effects of resistance exercise have shown to be long-lasting. This was previously attributed solely to motor learning, but more recently a memory mechanism residing in the muscle cell itself has been proposed, based on the novel observation that the myonuclei acquired by a former hypertrophic stimulus, remain in the muscle cell during long periods of detraining and may promote subsequent hypertrophy when an additional stimulus is provided. As such a cellular muscle memory has previously only been found in mice subjected to testosterone treatment, the purpose of the present study was to investigate whether a similar mechanism exists in humans and rats subjected to resistance exercise. The present study utilized a protocol of conventional resistance exercise as training and retraining periods in humans, while training and retraining through housing in a climbing cage was used to resemble strength training in rats. To maximize the hypertrophic response in rats, retraining was also performed by synergist ablation. Changes in muscle fiber size and myonuclear number was examined on isolated single fibers in humans and on cross sections in rats before and after training, detraining and retraining. In the present study, the human resistance exercise protocol turned out to be unsuitable for testing the cellular muscle memory hypothesis, due to a lack of myonuclear addition during training. The rat climbing protocol, however, caused a significantly higher myonuclear number in trained compared to untrained rats. This elevated number of myonuclei was maintained during detraining, indicating a long-lasting effect. When these muscles were subjected to retraining by synergist ablation, they showed an increased hypertrophic response compared to previously untrained muscles, thus suggesting the existence of a cellular memory mechanism in the skeletal muscles of rats previously subjected to resistance exercise by climbing.