In the present study the antioxidant and neuroprotective effects of insulin and lycopene on passive avoidance memory, total antioxidant capacity (TAC), malondialdehyde activity (MDA) and prevention of apoptosis in the hippocampus streptozotocin-induced diabetic rats were examined. The rats were randomly divided to six experimental groups (n=8 per group): Non-diabetic (controls); diabetic; diabetic treated with lycopene; diabetic treated with insulin; diabetic treated with lycopene and insulin; and normal treated with lycopene. Intraperitoneal injection of single dose (60 mg/kg) streptozotocin (STZ) was used to induce the diabetes rat model. The shuttle box test was used for learning and memory assessment. Rats were then sacrificed and hippocampi tissue isolated from the two hemispheres to determine TAC and MDA. Apoptosis rate was also evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling and acridine orange staining assays. The results indicated that lycopene and insulin, solely or in combination, prevented hippocampal neuronal cell death and improved learning and cognition by increasing TAC and decreasing MDA. Collectively, the findings presented herein suggest that insulin and lycopene co-treatment has neuroprotective effect, and ameliorates STZ-induced learning and memory impairment and apoptotic cell death in the hippocampal regions of diabetic rats.