Introduction: The aim of present study was to evaluate the effects of aerobic training and detraining periods on metabolic risk factors, BDNF and memory function. Materials and Methods: Forty-two middle-aged, sedentary males volunteers were randomly divided into four groups MetS Exercise (ME), MetS Control (MC), Healthy Exercise (HE) and Healthy Controls (HC). Both the ME and HE groups participated in an exercise training (AT) program (6 weeks), followed by 6 weeks of detraining (DT). Midterm and Digit Span memory tests and blood sampling were conducted before and after training and also following detraining. Data were analyzed using Pearson coefficient, multivariate ANOVA and ANCOVA and repeated measure. Results: Most of the metabolic risk factors significantly improved after AT in the ME group waist circumference and FBS however returned to baseline values following DT (P<0.05). Waist circumference and triglycerides in the HE group decreased significantly, but returned to baseline values after DT (P<0.05). Aerobic exercise training could ameliorate overall MetS Z scores in both the ME and HE, groups, effects that disappeared in the ME group, even following DT (P<0.05). Serum BDNF was significantly elevated in HE, but surprisingly decreased in ME, effects that both disappeared after DT (P<0.05). Only in HE, both the short-term and mid-term memory improved significantly after AT (P<0.05). Conclusion: These findings indicate that physical fitness training programs ameliorate metabolic risk factors and improve learning and memory ability.