Social isolation (SI) is related to adverse neurobehavioral effects and neurochemical changes when it occurs early in development. On the other hand, environmental enrichment (EE) is associated with a reduction in anxiety‐like and depression‐like behavior, as well as an increase in serotonin (5‐HT) levels in the prefrontal cortex and hippocampus in rodents. This study systematically reviewed the effects of SI and EE on emotional behavior and serotonergic system components in rats after weaning. Primary experimental studies that used subgroups of rats subjected to SI, EE, and normal social conditions after weaning were considered eligible. Studies that used transgenic rodents, ex vivo studies, in vitro studies, human research, or in silico studies were ineligible. Two authors completed searches in Medline/PubMed, LILACS, Scopus, Web of Science, EMBASE, and Open Gray. The Kappa index was calculated to assess agreement between reviewers and assess study quality. The results showed that the animals exposed to EE showed better adaptation to a new environment. Furthermore, EE increased 5‐HT levels in the hippocampus and prefrontal cortex of rodents. Thus, it appears that an EE during the critical period of development may reduce anxiety/depression‐like behaviors, as well as increase long‐term neurotransmitter response.