Background: Amyloid Beta (1-42) is derived from amyloid precursor protein and plays a critical role in AD pathogenesis. The purpose of this study was to investigate the effect of 6 weeks of voluntary wheel running on brain Amyloid beta (1-42) in the diabetic rats induced with alloxan. Materials and Methods: 28 male rats weight 185±1 were assigned randomly to 4 groups (N=7): normal control (C), training (T), control-diabetic (CD) and diabetic-training (DT). Diabetes was induced with injecting Alloxan (120 mg/kg dissolved in saline) intraperitoneal. Results: 6 weeks of voluntary wheel running decreased the cortex Aβ1-42 in T and DT groups. Aβ1-42 levels significantly decreased in the T and DT in compare with C and CD (p<0.001), respectively. Also Aβ1-42 levels significantly increased in the CD in compare with C (p<0.001). Conclusion: voluntary exercise had positive effects on decreasing of Aβ1-42 levels during 6 weeks. Therefore it can be recommended as therapeutic strategy for diabetes.