Chlorpyrifos (CPF), as an extensively used organophosphorus pesticide, has many toxic hazards on health. There is a lack of data regarding the toxic effect of CPF on Gut. Aim of the work: to investigate the toxic effect of chronic oral exposure to chlorpyrifos on jejunum of adult male albino rats and to evaluate the ameliorative role of propolis. Methodology: The study extended for 12 weeks and included fifty male albino rats that were divided into 4 groups as follows: control group (I) consisted of 20 rats equally and randomly subdivided into 2 subgroups: Ia (-ve control) & Ib (+ve control). propolis group (II) 10 rats treated with 400 mg/kg body weight of propolis dissolved in corn oil by oral gavage. chlorpyrifos group (III): 10 rats treated with CPF at a daily dose of 6.75 mg/kg {1/20 of the oral LD50 of CPF (135mg/kg)} dissolved in corn oil. CPF+propolis group (IV) 10 rats each was gavaged orally with CPF (6.75 mg/kg body weight) with simultaneous administration of propolis (400 mg/kg body weight) once daily. The levels of serum citrulline, circulating endotoxin core antibodies (Endocab IgG) were assessed, GSH & MDA in jejunal mucosa were measured. Histopathological and morphological analysis of the jejunal mucosa was also evaluated. Results: Significant decrease in serum citrulline level, increase Endocab IgG with a significant decrease in tissue GSH and increase in MDA in CPF group when compared with control and CPF+Propolis groups with disruption of jejunal epithelium and decrease in both height and width of villi. CPF+propolis group showed no significant difference in MDA levels when compared with control, but significant difference regarding other biochemical and histopathological parameters was detected on comparison with CPF group. Conclusion: CPF induced disruption and increased permeability of epithelial barrier in the jejunum with bacterial translocation and chronic endotoxemia evidenced by Endocab IgG. This may be due to induction of oxidative stress. Propolis as a natural, cheap and available product could partially ameliorate the toxic effect of CPF on jejunum.