Objective To investigate whether Adiponectin is involved in the protective effect of myocardial ischemia reperfusion (MIR) in mice pretreated with Sevoflurane.Methods Wild C57BL/6 male mice were randomly divided into three groups, each group had 10 mice: sham (sham Operation Group), MIR-control (model group), and MIR-Sevopre (pretreatment group). Male adiponectin knockout C57BL/6 （APN KO） mice were randomly divided into 4 groups, each group consisted of 10 Mice: KO-sham (knock-gene sham Group), KO-MIR-Control (knock-gene-Model-Group), KO-MIR-Sevopre (knock-gene-model-pretreatment-Group), and KO-Sevopre-adiporon-MIR (knock-gene-pretreatment-drug-group). The concentration of high, middle, and low molecular weight adiponectin in plasma of C57BL/6 mice in three groups was detected at 12h after modeling or control treatment. The swimming rate and swimming latency of C57BL/6 mice in three groups were detected at 24h after modeling or control treatment by Morris water maze. The incubation period of mice in APN KO four groups was detected on the 1st, 2nd, and 4th day after modeling or control treatment.Results The swimming rates of C57BL/6 mice in the three groups were compared on the 1st, 2nd, and 4th day after model replication. The repeated measurement design was used to analyzed the results, which showed: (1) There was no difference in the swimming rates of mice at different time points (P > 0.05); (2) There was no difference in swimming speed among the three groups (P > 0.05); (3) There was no difference in the trend of swimming speed among the three groups (P > 0.05). The latency of C57BL/6 mice in the three groups was compared on the 1st, 2nd, and 4th days after model replication. The repeated measurement design was used to analyzed the results, which showed: (1) there were differences in the latency of mice at different time points (P < 0.05); (2) The latency of the three groups was different (P < 0.05). Compared with sham group, the latency of MIR-Control group was longer (P < 0.05), and the latency of MIR-Sevopre group was shorter compared with MIR-Control group (P < 0.05); (3) There were differences in the change trend of incubation period among the three groups (P < 0.05). Compared with the plasma adiponectin levels of C57BL/6 mice in the three groups, there was significant difference in total adiponectin, high molecular weight adiponectin, and medium molecular weight adiponectin (P < 0.05), but there was no significant difference in low molecular weight adiponectin (P > 0.05). The latency of sham group was negatively correlated with plasma adiponectin level (r = -0.480, P =0.033), that of MIR-Control group was negatively correlated with plasma adiponectin level (r = -0.300, P = 0.040), and that of MIR-Sevopre group was negatively correlated with plasma adiponectin level (r = -0.730, P = 0.019). The latency of APN KO mice in 4 groups was compared on the 1st, 2nd, and 4th day after model replication. The repeated measurement design was used to analyzed the results, which showed: (1) There were differences in the latency of mice at different time points (P < 0.05); (2) The latency of the four groups was different (P < 0.05). Compared with the KO-sham group, the latency of the KO MIR-Control group was longer (P < 0.05), the latency of the KO MIR-Sevopre group was no difference compared with the KO MIR-Control group (P > 0.05), and the latency of the KO MIR-Sevopre-Adiporon group was shorter and compared with the KO MIR-Sevopre group (P < 0.05); (3) There was no difference in the change trend of incubation period among the four groups (P > 0.05).Conclusion Plasma adiponectin is involved in the protective effect of Sevoflurane pretreatment against MIR injury in mice. AdipoRon can take the place of Adiponectin in the protective effect of Sevoflurane on brain cognition after myocardial ischemia reperfusion in mice.