Diazinon (DZN) is one of the most broadly used organophosphorus insecticides in controlling agricultural pests, increasing exposure to these compounds that may have harmful side effects. Hesperidin (HN) is a citrus bioflavonoid with gifted anti-inflammatory and anti-oxidant effects. The purpose of this study was to explore antioxidant and anti-inflammatory effects of HN on DZN induced hepatotoxicity in adult male albino rats. Forty-eight adult male albino rats were included into four groups; Group I served as the control (IA, IB and IC), Group II HN (50 mg/kg), Group III diazinon (20 mg/kg) and Group IV hesperidin and diazinon in doses as previously mentioned. All treatments were given daily via oral gavage for 6 weeks. Subsequently, Blood samples were collected and serum liver enzymes (ALT and AST) were determined. Then livers were extracted to assess hepatic malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), histopathological (Haematoxylin and Eosin staining) and immunohistochemistry using tumor necrosis factor-α (TNF-α). Diazinon intoxication induced a significant raise of serum liver enzymes and hepatic MDA and a significant reduction in hepatic SOD and GSH. It also induced histopathological alterations in liver with strong TNF-α immunoreactivity. The previous toxic effects were partially improved by hesperidin treatment in combination with DZN. It can be concluded that HN supplementation alleviates DZN induced hepatotoxicity via antioxidant and anti-inflammatory properties.