The Nile rat (NR) models diet‐induced human type 2 diabetes (T2DM). In previous experiments (Brit J Nutr 106:1664, 2011), palm fruit juice (PFJ) blocked T2DM in male NR, while untreated rats exhibited advanced disease stages. The molecular mechanisms whereby PFJ exerts anti‐diabetic effects are unknown, prompting microarray gene expression analysis. Livers were obtained from NR undergoing 4 diet plans: hiCHO alone (diabetic control), 4800ppm resveratrol (RES) in food, 4800ppm PFJ in food, or 1500ppm PFJ in drinking water. Compared to hiCHO (most diabetic), hepatic liver gene expression profiles were enhanced for RES and PFJ‐food, while PFJ‐water gene expression changes were subtler. Random blood glucose was lowered (p<0.05) in both PFJ groups, but only slightly by RES (n.s.). Compared to hiCHO, PFJwater had 17 genes up‐regulated, 29 down‐regulated. PFJ‐food had 71 genes up‐regulated, 108 down‐regulated. RES had 90 genes upregulated, 76 down‐regulated. As a preliminary observation, the insulin signaling pathway, especially phosphatidylinositol (PI) 3‐ kinase, was significantly down‐regulated by PFJ‐food and RES, PFJ‐water being less marked. PI 3‐kinase has been reported to suppress glucose‐stimulated insulin secretion (Diabetes 51:87, 2002), suggesting PFJ and RES may modulate this activity in NRs to favor insulin secretion.Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board