Abstract: Background and Objective: Clinical application of anesthetics in neonatal or children causes neuronal degeneration. Present study evaluates the neuroprotective effect of barbaloin against anesthetic induced neuronal injured rats and also postulates the possible mechanism of its action. Materials and Methods: Animals on P7 were exposed for 6 h with 30% of oxygen that contain 0.75% of isoflurane and rats were treated with barbaloin 10 and 20 mg kg–1, p.o. for the duration of 21 days. Cognitive function was evaluated by using morris water maze (MWM) and level of mediators of inflammation and oxidative stress were estimated in the brain tissue by using enzyme-linked immunosorbent assay (ELISA). Moreover western blot assay was performed for the determination of expression of proteins in the neuronal tissues and apoptosis of neuronal cells were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Fluro Jade B staining. Results: Data of report suggest that barbaloin promotes the cognitive function by MWM and apoptosis of neuronal cells was also found to be reduced in barbaloin treated group than isoflurane (INF) group. There was decrease in the mediators of inflammation and oxidative stress in barbaloin treated group compared to INF group. Moreover western blot assay data reveals that barbaloin ameliorates the altered expression of JNK, ERK-1/2, Bcl-2, PI3K, Akt, BDNF and TrKB proteins in the brain tissues of anesthetic induced neuronal injured rats. Conclusion: Data of the report reveals the protective effect of barbaloin against isoflurane induced neuronal injured rats by regulating BDNF/Bcl-2/PI3K signaling pathway.