Brain derived neurotrophic factor (BDNF) is postulated to be an important mediator of exercise-induced neuroprotection. We tested the hypothesis that resistance exercise elevates circulating BDNF. Twenty healthy untrained college-aged males underwent a 5-week traditional or eccentric-enhanced progressive resistance training intervention. Blood was acquired at rest and 1, 30, and 60 min following a standardized resistance exercise testing bout performed at baseline and at the completion of the intervention. Serum BDNF responses did not differ between the two groups at any time point during baseline or post-intervention testing; thus, all values were combined into a single cohort for further analysis. Resting BDNF was not altered by the exercise training intervention [23,304 ± 1835 pg/ml (baseline) vs. 19,433 ± 1992 pg/ml (post-intervention)]. Following the baseline resistance exercise bout, serum BDNF increased 32% (p < 0.05) and was gradually reduced to 41% below resting levels at 60 min into recovery (p < 0.01). During post-intervention testing, serum BDNF increased 77% in response to the standardized resistance exercise bout (p < 0.01) and returned to resting values within 30 min. Ultimately, the change in serum BDNF from rest to immediately post-exercise was 98% greater at post-intervention than at baseline (p < 0.05). Our study is the first to demonstrate that resistance exercise induces a robust, yet transient, elevation of circulating BDNF and that progressive resistance training augments this response; perhaps demonstrating one mechanism through which exercise influences brain health.