The primary metabolize of chlorpyrifos (CPF) is in the liver tissue, which it can cause oxidative damage and apoptosis in liver cells. The use of exercise with antioxidant supplements could have a protective effects in the liver tissue especially by improve mitochondria function. The aim of the present study was to investigate the protective effect of aerobic exercise and eugenol (Eu) supplementation on destructive effects of CPF in liver tissue. Sixty-four adult male albino rats were randomly divided into eight groups (eight rats in each group). Four experimental groups received intraperitoneal injection of either 3.0 mg/kg body weight CPF in dimethyl sulfoxide for six consecutive weeks. Aerobic exercise was performed 5 days per week over 4 weeks for exercise groups. Finally, the animals were sacrificed for the histomorphometric analysis and biochemical measurement in the liver tissue. The result of this study show that consumption of CPF alone, caused collagen deposition, increased apoptosis, tumor necrosis factor α, malondialdehyde, and decreased catalase, superoxide dismutase, acetylcholinesterase (AChE) compared to control and exercise groups