Abstract Purpose To evaluate the neuroprotective effect of L-alanyl-glutamine in a gerbil model of brain ischemia-reperfusion injury based on immunohistochemical quantification of pro-inflammatory and cell activation biomarkers (TNF-α, NF-κB, IL-6 and HO-1). Methods Male gerbils weighing 100-180 g were pretreated with either 0.75 g/kg L-Ala-Gln (n=18) or 2.0 mL saline (n=18) administered i.v. 30 minutes before the bilateral ligation of the common carotid artery during 15 min and then the ligation was removed. Under anesthesia with urethane, brain tissue was harvested at 0 min (T0), 30 min (T30) and 60 min (T60) after reperfusion. The tissue was embedded in 10% formalin overnight and 4-μm sections were prepared for immunostaining with monoclonal antibodies. Immunostained cells were counted by optical microscopy. The statistical analysis used mean values based on 4 sections. Results The pretreatment with L-Ala-Gln animal group 1 demonstrated significantly lower levels of TNF-α, NF-κB and IL-6. On the other hand, the levels of HO-1 were significantly higher, suggesting a protective role in model of brain ischemia-reperfusion injury. Conclusion These findings suggest a protective effect of L-Ala-Gln by decreasing levels of TNF-alpha, IL-6 and NF-κB and Increasing levels of HO-1.