The aim of this paper was to examine in a prospective study the contribution of lifestyle risk factors and excess adiposity to the association between family history of diabetes and risk of type 2 diabetes. The analyses were performed on data from 73,227 women who participated in the Nurses’ Health Study cohort with 20 years of follow-up. Results showed a direct association between family history of diabetes and incidence of type 2 diabetes. However, an important part (21%) of this association was explained by the higher body mass index (BMI) observed among individuals with a family history of diabetes. Certain dietary factors such as lower alcohol consumption and higher intake of red meat and sugar-sweetened beverages also modestly contributed to the association. These results suggest that excess adiposity partly explains the association between family history of diabetes and risk of type 2 diabetes. Further research is needed to identify additional variables that mediate this association.