BackgroundAccompanying dramatic increase in obesity, the incidence of type I diabetes (T1D) is rapidly increasing. The objective of this study is to explore impacts of maternal obesity (MO) on the incidence of T1D in female offspring using non‐obese diabetic (NOD) mice.Methods4‐wk‐old female NOD mice were randomly separated into two groups and fed a control or a high fat diet for 8 weeks before mating. Mice were maintained at their respective diets during pregnancy and lactation. All offspring were fed the control diet after weaning till necropsy at age of 16 weeks.ResultsFemale offspring (16wk‐old) born to obese dams showed increased body weight and respiratory exchange ratio, more severe islet lymphocytes infiltration (insulitis), accompanied with elevated p65 inflammatory signaling and TNFá protein in pancreas. In addition, MO resulted in impaired glucose tolerance and low serum insulin level in offspring, which was associated with increased phos‐AMPK and phos‐ACC.ConclusionMO resulted in exacerbated insulitis and inflammation in pancreas of NOD offspring mice, accompanied with impaired glucose intolerance and decreased insulin level. For the first time, data show that MO negatively impacts incidence of T1D in offspring, providing a possible explanation for the increased incidence of T1D in children. NIH 1R15HD073864; INBRE P20RR016474; USDA 2008–35203‐19084; 2009–65203‐05716