Impaired neuroplasticity and altered connectivity between different brain regions may be key features of depression. As the cytokine erythropoietin (EPO) increases brain derived neurotrophic factor (BDNF) levels, EPO may enhance neuron survival and growth, leading to antidepressant effects. Here, EPO was tested for its ability to reverse depressive-like symptoms in rats following three weeks of chronic mild stressors. Neither stressor exposure nor EPO affected sucrose preference, which has been used to model the anhedonia characteristic of depression. Additionally, EPO did not reverse stressor-induced social avoidance. BDNF mRNA expression was reduced by stressor and EPO treatments in the prefrontal cortex, and elevated in the amygdala with EPO treatment. Additionally, FGF-2 expression was reduced in the amygdala with stressor exposure, but normalized following EPO treatment. Many of the results are inconsistent with a priori hypotheses, possibly owing to factors such as the timing of tissue collection and a lack of environmental enrichment.