Objectives: This study was to investigate the effect of long term insulin treatment on adverse postischemic cardiac structural and functional changes.Methods: Adult male rats were subjected to myocardial ischemia (MI) and received one of the following treatments: control, insulin (0.5 U/ml, 1 ml/kg·d-1, i.h., for 4 weeks), insulin plus wortmannin (15 μg/kg), or insulin plus SB239063 (30 mg/kg).Results: MI rats receiving long term insulin treatment showed smaller systolic left ventricle cavity (LVs) and thicker systolic interventricular septum (IVS), and increased ejection fraction (EF) (P<0.05).Moreover, insulin treatment increased Akt but inhibited p38 MAPK phosphorylations, and increased the plasma brain natriuretic peptide (BNP) levels though did not change the BNP mRNA levels.These effects of insulin Were not blocked by the PI3K inhibitor wortmannin, and could not be further strengthened by the p38 MAPK inhibitor SB239063.Conclusions: Insulin improves postischemic cardiac structural and functional changes via inhibiting p38 MAPK activation and thus increasing plasma BNP level.