Objective To explore the related factors of insulin sensitivity in infants and toddlers. Methods From January 2006 to May 2008, 246 infants and 120 toddlers who had regular physical check-ups at the Children Healthcare Center of Third Hospital of Peking University were selected in this retrospective study. The homeostasis model assessment insulin resistance index (HOMA-IR), insulin action index(IAI), fasting glucose-to-insulin ratio (FGIR) and HOMA-β cell function (HOMA-β) were measured with the homeostasis model analysis. According to different glucose metabolic situation of the pregnant mothers and diabetes family history, the infants and toddlers were divided into different groups. The above indicators were compared among groups.Results In infants with maternal diabetes, the levels of HOMA-IR and HOMA-β were 3.24 (2.76-4.12) and 164. 00 (114. 44-192.85), higher than those born to mothers without abnomal glucose metabolism [1.51 (0. 86-2.50) and 67.07 (41.83-106.22)], while the levels of IAI and FGIR were lower[-7.18(-7.41-7.02) and 7.31(5.82-8.55) vs -6.41(-6.92-5.85) and 14.84(9.49-24. 79)] (Z=3. 76,3. 35,3. 76 and 3.71, P＜0. 017). Compared with infants of maternal impaired glucose tolerance,the level of HOMA-IR was higher (Z= 3.19, P＜0.017) in infants with maternal diabetes,the level of IAI was lower(Z= 3. 19, P＜0. 017). No significant difference of insulin sensitivity were observed between infants with and without maternal impaired glucose tolerance (P＞0. 017). The level of HOMA-IR was higher in infants and toddlers with diabetes in first-degree relatives [infants: 3.24(2. 73-4. 13) vs 1.41(0.84-2.50) ; toddlers: 3.98(2.62-4.80) vs 1.70(0.92-3.04); P＜0. 017], while the levels of IAI and FGIR were lower [infants: IAI, -7. 18(-7.42-- 7.00) vs - 6.34 ( - 6.91- 5.82); FGIR, 7.31 (5.40-7.48) vs 14.87 (9.53-25.17); toddlers: IAI,-7.38(-7.57-6.97) vs -6.54(-7.11-5.92); FGIR, 6.17(6.04-8.00) vs 12.65(8.33-21.53), P＜0. 017], and the level of HOMA-β was higher just in the infants [164.00(137.82-198.00) vs 67.06(40.40-106.83), P＜0. 017]. No significant difference was observed in infants with second-degree relatives diabetes and without diabetic family history group (P＞0. 017). Conclusions Maternal diabetes and diabetic family history in first-degree relatives were significantly related to the decrease of insulin sensitivity in infants and toddlers.