Abstract: Objective　To investigate the expressions of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) in adipocytes during catch-up growth in neonatal rats with intrauterine growth restriction (IUGR) and their correlations with the insulin resistance. Methods Sprague-Dawley rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30% of food amount consumed in control group every day through the whole pregnant period to establish IUGR animal model, and were fed increased amount of breastmilk from postnatal day 1 to 21 to establish the period of catch-up growth in IUGR animal model (IUGR-CG). Fasting serum glucose, insulin and triglyceride were measured in blood from heart ventricles of 4-week old SD rats and insulin resistance index was calculated. Pre-adipocytes and mature adipocytes were obtained from SD rats at different age (1-week, 3-week, 5-week and 7-week old) and the former were induced to differentiate toward mature adipocytes. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-Time PCR and Western blot. Results The expression levels of IRS-1, IRS-2 mRNA in mature adipocytes of IUGR-CG rats were significantly lower than those of IUGR rats at 5-weeks and 7-weeks old (P<0.05) while the expression levels of IRS-1, IRS-2 mRNA in differentiated adipocytes of IUGR-CG rats were significantly lower than those of IUGR rats at 5-weeks old (P<0.05). The expression levels of IRS-1, IRS-2 protein in two kinds of adipocytes (mature and differentiated adipocytes) of IUGR-CG rats were significantly lower than those of IUGR rats from postpartum week 1 through 7 (P<0.05). Conclusions IRS-1 and IRS-2 expression levels are downregulated in adipocytes during catch-up growth of IUGR rats, which may be closely related with insulin resistance.