Objective(s): This study aims to investigate the role of putrescine against brain ischemia-reperfusion (IR) injured rats administered with 250 µmol/kg exogenous putrescine and highlight the IR-associated mechanisms in energy metabolism and inflammatory pathway. Materials and Methods: The rats were divided into six groups: 1-Sham group; 2-IR group, 30 min of ischemia and 30 min of reperfusion was performed with bilateral carotid occlusion (BCAO); 3-IPR group, a single oral dose of putrescine was administered at the start of the 30-minute reperfusion; while in the other treatment groups, 4 doses of putrescine were given within 12-hour intervals. After 30 min of reperfusion, the first dose was administered immediately in the IR-PI (group 4), after 3 hr in IR-PII (group 5), and after 6 hr in IR-PIII (group 6). Interleukin-6 (IL-6), Nuclear factor NF-kappa-B (NF-kB), Adenosine triphosphate (ATP), total Nitric oxide (NO), 8-hydroxyguanosine (8-OHdG), Spermidine/Spermin N-acetyltransferase (SSAT) levels were analyzed in brain tissues. Results: IR reduced brain ATP levels; however, putrescine treatment reversed this state. Brain NO and 8-OHdG levels, and NF-kB and IL-6 levels increased significantly in the IR group and these elevations were decreased in putrescine administered groups. SSAT levels were higher in the IR-PII group. The lowest levels were observed in the IR-PIII group. Conclusion: The exogenous putrescine supplementation after cerebral IR creates neuroprotective effects independent of the time of administration; according to conditions such as formation of radicals in the brain, the spread of the inflammation and the need for consumption of energy are considered as a whole.