Purpose: This study aimed to evaluate and identify the value and explore the mechanisms of Angiogenic Factor with G-patch and FHA domains 1 (AGGF1) in postoperative cognitive dysfunction (POCD). Methods: Rats were separated into four different groups, namely sham, isoflurane, isoflurane ţ recombinant human Aggf1 (rh-Aggf1) (5 mg kg1), and isoflurane ţ rh-Aggf1 (10 mg kg1). qPCR and western blot assays were applied to detect the correlation between the expression of AGGF1 and isoflurane administration. Then, the Morris water maze (MWM) test was applied to evaluate the effect of AGGF1 on improving the POCD rats. Subsequently, TUNEL assay was applied and the cell apoptosis-related proteins were tested to reveal the antiapoptotic effect of AGGF1 in POCD rats. Furthermore, the mRNA and protein levels of TNF-a, IL-6, and IL1b were also detected by qPCR and ELISA to verify the anti-inflammatory effects of AGGF1 on POCD rats. Besides, the protein expression levels of PI3K, Akt, and NF-kB in each group were examined by western blot. Results: In this study, the results revealed that isoflurane induced a decrease in AGGF1 expression in the hippocampus of aged rats. In addition, exogenous AGGF1 attenuated POCD in aged rats. Meanwhile, exogenous AGGF1 had anti-apoptotic and anti-inflammatory effects in POCD rats. Further research indicated that AGGF1 activated the PI3K/Akt pathway. Conclusion: AGGF1 has neuroprotective effect against isoflurane-induced cognitive dysfunction in aged rats via activating the PI3K/AKT signaling pathways.  Kulcsszavak: AGGF1, POCD, PI3K, AKT, isoflurane, aged rats