The present study was performed to investigate the protective effects of zinc (227 mg/L in drinking water) treatment in chlorpyrifos (13.5 mg/kg body weight, orally) induced hepatotoxicity in male rats. Animals received chlorpyrifos and/or zinc treatments for 8 wk. A 99mTc-mebrofenin clearance test was done to determine the biological half-life (Tbiol) of the radiopharmaceutical in liver for the determination of the hepatobiliary function of the animals. At the end of treatment periods, samples were collected for the measurement of zinc levels in serum and liver. Electron microscopic studies were performed to study hepatic ultrastructure following various treatments. When compared to normal controls, chlorpyrifos treatment resulted in reduced hepatic and serum zinc levels (pT biol) of 99mTc-mebrofenin in liver was increased (pT biol values of 99mTc-mebrofenin within normal limits. Zinc treatment also protected hepatocytes from the marked disruptions in the membranous organelles and narrowing/blocking of biliary channels, which was otherwise a common observation following chlorpyrifos treatment. These data clearly show the protective effects of zinc in animals subjected to organophosphate poisoning.