Oral sub-acute toxic effects of chlorfenapyr alone and its interaction with fluoride was studied in wistar rats. Chlorfenapyr administered @ 96.8mg/kg daily for 28 days decreased cholinesterase and protein activity but elevated biochemical indices like phosphatases (ACP & ALP), aminotransferases (AST & ALT) in plasma. At 48.4mg/kg dose it enhanced plasma aminotransferases and ALP. Either daily dose of chlorfenapyr was capable of inducing peroxidation of erythrocyte membrane with decline in its glutathione levels. Decrease in the activities of other oxidative stress enzymatic components like SOD, GPx, was observed at higher dose. These changes get more pronounced with co-exposure of fluoride. The results revealed the potential of chlorfenapyr to induce oxidative hepatic damage due to altered oxidative stress parameters in hepatic tissue as well as by histopathological change such as swelling of central vein & hepatocyte degeneration. Such changes were more pronounced when rats were co-exposed to fluoride and chlorfenapyr.