DZN is one of the most crucial organophosphorus (OPs) compounds that is widely utilized in agriculture and horticulture to manage pests and boost crop output. . Our experiment evaluated the protective and antioxidant potential of sesame oil (Ses.oil) against DZN toxicity on the jejunum of albino rats. Forty mature male albino rats were divided randomly into four groups, . Group (a) Control group: received 1ml/kg of normal saline by oral gavage daily for 4 weeks. Group (b) Sesame oil group: received 4 ml/kg of sesame oil daily for 4weeks. Group (c) DZN treated group: received DZN (20 mg/kg body weight) by oral gavage daily for 4weeks. Group (d) DZN-Sesame oil group: a dose of 20 mg/kg DZN plus 4 ml/kg of sesame oil daily for 4weeks. Rats were weighed and the jejunal tissues were obtained for biochemical analysis to measure jejunal malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and nitric oxide (NO), for Histopathological examination (Hematoxylin and Eosin staining, PAS and bromophenol blue stain) and immunohistochemistry using (TNF-α and E-cadherin). Diazinon intoxication induced a decrease in rats’ body weight and intestinal oxidant/antioxidant imbalance (an increase in NO and MDA and a reduction in SOD and GSH). Also, DZN induced histopathological changes in the jejunum with strong expression of TNF-α immunoreactivity and low expression of E-cadherin immunoreactivity. The previous toxic effects were improved by Ses.oil treatment when administered in combination with DZN. This study has revealed that Ses.oil supplementation alleviates DZN toxicity via its antioxidant and anti-inflammatory properties.