The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Delta(9)-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Delta(9)-THC treated, (3) diabetic, and (4) diabetic + Delta(9)-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Delta(9)-THC and Delta(9)-THC treated diabetic groups received 3 mg/kg/day of Delta(9)-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin-biotin-peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic + Delta(9)-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic + Delta(9)-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes + Delta(9)-THC group showed a decrease compared to the diabetic group. These results indicate that Delta(9)-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats. (C) 2013 Elsevier GmbH. All rights reserved.