Background: The literature regarding the relation between egg consumption and type 2 diabetes (T2D) is inconsistent and there is limited evidence pertaining to the impact of egg consumption on measures of insulin sensitivity. Objective: The objective of this study was to investigate the effect of dietary whole egg on metabolic biomarkers of insulin resistance in T2D rats. Downloaded from https://academic.oup.com/cdn/advance-article-abstract/doi/10.1093/cdn/nzz015/5374517 by Iowa State University user on 28 March 2019 Methods: Male Zucker diabetic fatty rats (n=12; 6 wk of age) and their lean controls (n=12; 6 wk of age) were randomly assigned to a casein- or whole egg-based diet. At wk 5 of dietary treatment, an insulin tolerance test (ITT) was performed on all rats and blood glucose was measured by glucometer. After 7 wk of dietary treatment, rats were anesthetized and whole blood was collected via a tail vein bleed. Following sedation, the extensor digitorum longus muscle was removed before and after an intraperitoneal insulin injection and insulin signaling in skeletal muscle was analyzed by western blot. Serum glucose and insulin were analyzed by ELISA for calculation of the homeostatic model assessment of insulin resistance (HOMA-IR). Results: Mean ITT blood glucose over the course of 60 min was 32% higher in ZDF rats fed the whole egg-based diet compared to ZDF rats fed the casein-based diet. Furthermore, whole egg consumption increased fasting blood glucose by 35% in ZDF rats. Insulin-stimulated phosphorylation of key proteins in the insulin signaling pathway did not differ in skeletal muscle of ZDF rats fed casein- and whole egg-based diets. In lean rats, no differences were observed in insulin tolerance, HOMA-IR and skeletal muscle insulin signaling, regardless of experimental dietary treatment. Conclusions: These data suggest that whole body insulin sensitivity may be impaired by whole egg consumption in T2D rats, although no changes were observed in skeletal muscle insulin signaling that could explain this finding.