Background: Alzheimer›, s disease (AD) is characterized by excessive deposition of the amyloid-β,peptide (Aβ, ) in the central nervous system and reducing its level is the goal of many medications. This study aimed to investigate the effect of aerobic training and omega-3 intake on Aβ, 42, neprilysin, and γ,-secretase levels in the hippocampus of male rats Alzheimer›, s model. Methods: Fifty male Wistar rats (age: 12 weeks-old and weight: 222. 31 ±,11. 91 g), were divided into the five groups including control Alzheimer’, s (AC), Alzheimer’, s with omega-3 intake (AO), Alzheimer’, s training (AT), Alzheimer’, s with omega-3 intake and training (AOT) and Healthy Control (HC). AD was induced by the injection of homocysteine (60mM) into the rat brain ventricle. Training on the treadmill with a speed of 20 m/min (60 minutes and 5 days/week) was applied. The supplement group received omega-3 supplement 800 mg/kg of body weight, daily for eight weeks. Levels of Aβ, 42, γ,-secretase, and neprilysin protein were measured using ELISA method. In data analysis, one-way ANOVA and Tukey test as post hoc were used (P < 0. 05). Results: The obtained results showed that the level of Aβ, 42 in the hippocampus of AC group was significantly higher than that of the HC group (P = 0. 001). Also, the level of Aβ, 42 in the hippocampus of AC group was significantly higher as compared to AO, AT, and AOT groups (P values 0. 001, 0. 007, and 0. 003 respectively). The γ,-Secretase level in the hippocampus of AC group was significantly higher than that in the HC group (P = 0. 001). Moreover, the γ,-secretase levels in the hippocampus of the AC group were significantly higher compared to AO, AT, and AOT groups (P values: 0. 002, 0. 001, and 0. 001 respectively). There was no significant difference in neprilysin levels of the hippocampus among the research groups (P = 0. 534). Conclusion: It appears that exercise training and omega-3 consumption, can affect amyloidogenic pathways through reducing the level of γ,-secretase, and lead to reduced level of hippocampus Aβ,in AD subjects. Therefore, aerobic exercise training and omega-3 intake can be studied as a complementary therapy in Alzheimer’, s patients.