Dimethoate is a widely used organophosphate insecticide known to be toxic to the pancreas. The aim of this study is to detect the possible protective effects of the fenugreek seed ethanolic extract on the biochemical, histological, and ultra-structural abnormalities induced by dimethoate chronic exposure in the pancreas of adult male rats. The study was conducted on 50 adult male albino rats that were divided equally into 5 groups: (group I) negative control, (group II) vehicle control group, (group III) fenugreek-treated group that was given 400 mg/kg ethanolic fenugreek seed extract once daily, (group IV) dimethoate group received 20 mg/kg/day dimethoate, and (group V) dimethoate- + fenugreek-treated group received a combination of dimethoate and fenugreek in the same previous doses. Dimethoate treatment caused a significant increase in serum glucose, amylase, and lipase levels and a significant decrease in serum insulin. A significant increase in lipid peroxidation and pro-fibrotic cytokine (TGF-β1) together with a significant reduction of the antioxidant {reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD)} activities and the anti-inflammatory (IL-4) in pancreatic tissues was also recorded. There was a histological and ultra-structural evidence of pancreatic acinar and islet cell injury. The recorded abnormalities were reversed in dimethoate+fenugreek treated group indicating that fenugreek ethanolic extract can serve as an antidote for dimethoate-induced pancreatic insult.