The present work was carried out to investigate (a) the potential of selected organophosphorus insecticides (OPI) viz., monocrotophos (MCP) and dimethoate (DM) to alter glucose homeostasis in rats (b) the effect of MCP pretreatment and post-treatment on diabetic outcome in experimentally-induced diabetic rats (c) the propensity of MCP to potentiate ‘insulin resistancemediated’ alterations in “high fructose diet” fed rats (d) the interactive role of experimental diabetes and OPI on oxidative balance and their toxic outcomes in in rats. Our study clearly established the potential of monocrotophos and dimethoate to affect glucose homeostasis in rats both after single and multiple dosing. While single dose of MCP did not affect the lipid profile, hepatic damage markers and liver glucose homeostasis in diabetic rats, multiple doses of MCP at different exposure regimes showed the propensity to aggravate the diabetic outcome in experimentally-induced diabetic rats by augmenting blood glucose levels, altering glucose homeostasis and parameters related to lipid profile, enhancing hepatic and renal damage. This study clearly provided evidences on the potential of monocrotophos to augment the diabetic complications and diabetic outcome in rats. Our study also established that pretreatment of rats with monocrotophos had the potential to aggravate outcomes in diabetic rats and hence pre-exposure to OPI may augment the diabetic outcome. We also demonstrated that monocrotophos possessed the propensity to augment alterations induced by High Fructose Diet (HFD) in rats which indirectly demonstrates the potential of OPI to augment secondary complications in animals with insulin resistance, hypertriglyceridemia and liver damage. Further, our studies revealed that monocrotophos per se has the potential to induce oxidative stress. Besides, it possesses the propensity to augment the oxidative damage in experimentally-induced diabetic rats as well as that in HFD rats. In conclusion, our findings suggest that people exposed to pesticides are more prone to diabetes or people who are diabetic are likely to exhibit exaggerated diabetic complications and outcome if exposed to organophosphorus insecticides.