Chlorpyrifos (CPF) is a conventional chlorinated organophosphate insecticide, it used widely to control a variety of pests in agriculture and animal farm. Acute and chronic exposure to CPF can elicit several adverse effects including oxidative stress and DNA damage. Twenty-eight rats were divided randomly into four groups of seven rats each. The first group was served as control and received distilled water. The second one received aqueous extract of propolis (100 mg/kg). The third group was administered 2.5 mg/kg of chlorpyrifos (1/30 LD50). The fourth group was received propolis two hours before CPF administration. All animals were orally intubated five days/week for four weeks. Results showed that oral administration of CPF led to a significant increase in liver enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) as well as malondialdehyde (MDA) level beside the percentage of DNA damage in liver tissue were increased in contrast with control group. Decrease in serum cholinesterase (ChE) activity as well as liver reduced glutathione (GSH) level, glutathione-S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were observed. Co-administration of propolis to CPFtreated group improved all biochemical parameters towards the control value although this treatment couldn't normalize it. The data provide evidence for co-administration of propolis to CPFtreated animals ameliorate the oxidative stress and DNA damage revealed the antioxidant property of propolis.