The aim of the present study was to develop an alternative non-obese non-genetic rat model of type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Caffeine 5 mg/kg BW + STZ (CAF5), Caffeine 10 mg/kg BW + STZ (CAF10), Caffeine 20 mg/kg BW + STZ (CAF20) and Caffeine 40 mg/kg BW + STZ (CAF40) and were fed a commercially available rat pellet diet and normal drinking water ad libitum throughout the 13 weeks experimental period. After a one week acclimatization period, diabetes was induced in the animals in DBC and all CAF groups with an injection (i.p.) of the respective dosages of caffeine (mg/kg BW) 15 min before the injection (i.p.) of STZ (65 mg/kg BW) when normal saline was injected to the DBC group instead of caffeine. The NC group received normal saline and citrate buffer instead of caffeine and STZ, respectively. One week after the STZ injection, animals with non-fasting blood glucose > 300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in the CAF5 and CAF10 groups were eliminated from the study due to the severity of diabetes and the experiment was continued with the remainder groups for a 13 weeks period. At the end of the experimental period the rats were euthanized and blood and organ samples were collected for subsequent analysis. The data of daily food and fluid intake, weekly body weight and blood glucose, oral glucose tolerance test, serum insulin, fructosamine, lipid profile, organ specific and antioxidative enzymes, anti-diabetic drug response tests, and liver, heart, kidney and pancreas histopathology suggest that the CAF20 group can be a new and alternative non-obese non-genetic chemically-induced model for T2D and can be therefore used for both chronic and acute research studies as well as pharmacological screening of new anti-diabetic drugs. / Thesis (M.Sc.)-University of KwaZulu-Natal, Durban, 2013.