Chlorpyrifos, a well known organophosphorus insecticide and heavy metal lead, was challenged to Wistar rats tostudy their interactive effects on biochemical parameters (clinical pathology) after acute exposure via oral gavaging.Hematology and clinical chemistry parameters were estimated after 14 days of exposure. In addition, serum butryland RBC cholinesterase was estimated on days 3rd and 15th of experimentation. The study was conducted using twodifferent dose levels of chlorpyrifos and lead acetate and grouped into seven groups. The parameters of hematologyand serum chemistry were analysed through automatic analyzers. No treatment related or interactive effects werenoticed in hematology values except for the reduced RBC, Hb content and HCT values in lead treated animals at1000mg/kg. A significant decrease in both serum and RBC cholinesterase enzymes were noticed in animals treatedwith chlorpyrifos at 50 mg/kg and in combination group (chlorpyrifos 50 + lead 1000 mg/kg), and increased inhibitionalong with delayed recovery was observed in the animals of combination group (i.e., chlorpyrifos plus lead).Chlorpyrifos in presence of lead increases the inhibition of both serum and RBC cholinesterase enzymes. The longlasting or persistence effects of CPF along with and lead may result in impaired cognitive functions of brainconsidering the role of cholinesterases in neuronal architecture of brain and other normal functioning of nervoussystem. Therefore, simultaneous exposure to a combination of chlorpyrifos and lead is considered to be moredangerous than to an exposure of either alone. In addition, serum chemistry revealed changes in concentrations ofglucose and sodium owing to lead treatment.