Severe and prolonged stress is the main environmental factor that precipitates depression, anxiety and cognitive dysfunctions. On the other hand, exposure to environmental enrichment (EE) has been shown to induce progressive plasticity in the brain and improve learning and memory in various neurological and psychiatric disorders. It is not known whether exposure to enriched environment could ameliorate chronic immobilisation stress-induced cognitive deficits and altered molecular markers. Hence, in the present study we aimed to evaluate the effect of enriched environment on chronic immobilisation stress (CIS) associated changes in spatial learning and memory, behavioural measures of anxiety, depression and molecular markers as well as structural alterations. Male Wistar rats were subjected to chronic immobilisation stress for 2 h/day/10 days followed by 2 weeks of exposure to EE. CIS resulted in weight loss, anhedonia, increased immobility, spatial learning and memory impairment, enhanced anxiety, and reduced expression of BDNF, VEGF, GFAP and glucocorticoid receptors (GR) in discrete brain regions. Interestingly, stressed rats exposed to enrichment ameliorated behavioural depression, spatial learning and memory impairment and reduced anxiety behaviour. In addition, EE restored BDNF, VEGF, GFAP and GR expression and normalized hypotrophy of dentate gyrus and hippocampus in CIS rats. In contrast, EE did not restore hypertrophy of the amygdalar complex. Thus, EE ameliorates stress-induced cognitive deficits by modulating the neurotrophic factors, astrocytes and glucocorticoid receptors in the hippocampus, frontal cortex and amygdala.