Urocortin 3 (Ucn 3), a member of the Corticotrophin-releasing Factor (CRF) family of peptides, is strongly expressed in mammalian brain, skeletal muscle, adipose tissue, and pancreatic β cells and has been shown to stimulate insulin secretion. The purpose of this study was to determine the expression of UCN3 levels in high-fat and fructose-induced type-2 diabetic rats'' visceral adipose tissue (VAT), also to investigate the UCN3 levels and insulin resistance relationship, and the show the effect of β-caryophyllene on UCN3 expression in high-fat and fructose-induced type-2 diabetic rats. Diabetic rats were generated by giving rats a high-calorie food composition with 2% cholesterol, 1% cholic acid, 30% coconut oil, 67% regular rat feed, and 25% fructose through drinking water for 9 weeks. Then the rats were treated with an oral effective dose of 200 mg of β-caryophyllene or 50 mg of quercetin (QCT)/kg b.wt. once a day for 30 days to find out whether ß-caryophyllene regulates URC3 expression. The data indicated that ß-caryophyllene treatment significantly decreased the mRNA and protein expression of urocortin-3 in diabetic rats, the same as the standard drug quercetin. β- Caryophyllene reduced the expression of urocortin-3 and the risk of insulin resistance in type 2 diabetes by reducing inflammation brought on by oxidative stress through β-caryophyllene''s antioxidant activity.