Lipoprotein lipase (LPL) catalyzes the peripheral hydrolysis and clearance of circulating triglycerides (TG). Its increase in adipose tissue and decrease in muscle following food intake are mediated by insulin. The present study aimed to assess whether adipose LPL becomes resistant to insulin in a nutritional model of resistance of glucose metabolism to insulin (insulin resistance, IR). Sprague-Dawley rats were fed for 4 weeks a non-purified diet (chow) or a purified high-sucrose, high-fat (HSHF) diet (each 40% of total energy), which induced overt insulin resistance, as assessed by a euglycemic-hyperinsulinemic clamp. Rats were fasted for 24 h and then refed for 1, 3, or 6 h with chow. The postprandial rise in plasma insulin levels was similar in both dietary groups, whereas glycemia was higher in HSHF-fed than in chow-fed animals, indicating glucose intolerance and insulin resistance. In chow-fed rats, LPL activity increased 2- to 4-fold between the 3^rd and the 6^th h of refeeding in inguinal, retroperitoneal and epididymal white adipose depots. In HSHF-fed rats, the postprandial increase in adipose LPL was minimal (30% at most). Muscle LPL decreased postprandially in HSHF-fed rats, suggesting maintenance of its sensitivity to insulin, but increased in chow-fed animals. Peak postprandial triglyceridemia at 3 h post-refeeding was significantly higher (+70%) in insulin resistant than in control rats. The postprandial rate of appearance of TG into the circulation was similar in control and insulin resistant rats, indicating that hypertriglyceridemia of the latter was due to impaired clearance. These results demonstrate that adipose LPL becomes resistant to the action of insulin in diet-induced IR, and that chronic HSHF feeding alters the postprandial modulation of adipose LPL by insulin. The findings further suggest that, under certain nutritional conditions, modifications in adipose LPL modulation associated with IR, along with low muscle LPL activity, heightens postprandial hypertriglyceridemia through attenuated TG clearance.