Extracorporeal membrane oxygenation (ECMO) could increase survival rate and neurological outcomes of cardiac arrest (CA) patients compared with conventional cardiopulmonary resuscitation (CCPR). Currently, the underlying mechanisms how ECMO improves neurological outcomes of CA patients compared with CCPR have not been revealed. A pig model of CA was established by ventricular fibrillation induction and then underwent CCPR or ECMO. Survival and hemodynamics during the 6 h after return of spontaneous circulation (ROSC) were compared. The levels of inflammatory cytokines and Ca2+-ATPase and NA(+)-K+-ATPase activities were detected. Brain tissues histology and ultra-microstructure in CCPR and ECMO groups were also examined. Results suggested that ECMO significantly improved the survival of pigs compared with CCPR. Heart rate (HR) decreased while cardiac output (CO) increased along with the time after ROSC in both ECMO and CCPR groups. At each time point, HR in ECMO groups was lower than that in CCPR group while CO and mean arterial pressure in ECMO group was higher than CCPR group. In ECMO group, lower levels of IL-1, IL-1 beta, IL-6, TNF alpha, and TGF beta, especially IL-1, IL-6, TNF alpha, and TGF beta, were found compared that in CCPR group while no difference of IL-10 between the two groups was observed. Similar with the results from enzyme-linked immunosorbent assay, decreased expressions of IL-6 and TGF beta were also identified by Western blotting. And Ca2+-ATPase and NA(+)-K+-ATPase activities were increased by ECMO compared with CCPR. Hematoxylin and eosin staining and ultra-microstructure examination also revealed an improved inflammation situation in ECMO group compared with CCPR group.